Triazoles as oxytocin antagonists

ABSTRACT

The present invention relates to triazole derivatives of formula (I) notably for use as pharmaceutically active compounds, as well as pharmaceutical formulations containing such triazole derivatives. Said triazoles are useful in the treatment and/or prevention of preterm labor, premature birth, dysmenorrhea, inappropriate secretion of vasopressin, congestive heart failure, arterial hypertension, liver cirrhosis, nephrotic syndrome and ocular hypertension. In particular, the present invention is related to triazole derivatives displaying a substantial modulatory, in particular antagonistic activity, of the oxytocin and/or vasopressin receptor. More preferably, said compounds are useful in the treatment and/or prevention of disease states mediated by oxytocin and/or vasopressin. The present invention is furthermore related to novel triazole derivatives as well as to methods of their preparation.

FIELD OF THE INVENTION

The present invention is directed to triazole derivatives, in particularfor use as medicaments, as well as pharmaceutical formulationscontaining such triazole derivatives. Said triazole derivatives areuseful in the treatment and/or prevention of preterm labor, prematurebirth, dysmenorrhea, inappropriate, secretion of vasopressin, congestiveheart failure, arterial hypertension, liver cirrhosis, nephroticsyndrome and ocular hypertension. Preferably, the triazole derivativesdisplay a modulatory, notably an antagonist activity of the oxytocinand/or vasopressin receptor. More preferably, said compounds are usefulin the treatment and/or prevention of disease states mediated byoxytocin and/or vasopressin, including preterm labor, premature birth,inappropriate secretion of vasopressin, congestive heart failure,arterial hypertension, liver cirrhosis, nephrotic syndrome, hypertensionand dysmenorrhea.

BACKGROUND OF THE INVENTION

Arginine vasopressin (AVP) and oxytocin (OT) are cyclic nonapeptideswhose actions are mediated by activation of specific G protein-coupledreceptors currently classified into V₁-vascular (V₁R), V₂-renal (V₂R)and V₃-pituitary (V₃R) AVP receptors, as well as OT receptors (OT-R)(1-2).

Oxytocin (OT) causes the contraction of the uterus of mammals duringlabor. The corresponding oxytocin receptor belongs to the family ofG-protein-coupled receptors and is similar to V₁ and V₂ vasopressinreceptors. OT receptors increase dramatically during the course ofpregnancy. The concentration of OT receptors has been shown to correlatewith spontaneous uterine activity (3-4). OT-induced contractions of theuterus during labor result in the dilatation of the cervix andeventually in the movement of the foetus through the vaginal canal. Insome cases, these contractions occur before the foetus is fully viable,resulting in premature labor. Premature labor and premature birth areundesired as they are major causes of perinatal morbidity. Hence, themanagement of preterm labor represents a significant problem in thefield of obstetrics.

Vasopressin, also called “antidiuretic hormone”, is a cyclic nonapeptidehormone that exhibits a series of physiological effects including freewater re-absorption, vasoconstriction, cellular proliferation andadrenocorticotrophic hormone (ACTH) secretion. In a healthy organism,vasopressin plays an important role in the homeostasis of fluidosmolality and volume status. However, in several diseases or conditionssuch as the syndrome of inappropriate secretion of vasopressin,congestive heart failure, arterial hypertension, liver cirrhosis,nephrotic syndrome, dysmenorrhea and ocular hypertension, vasopressin isassumed to play an important role (1, 5).

In recent years, strong evidence has accumulated indicating that thehormone oxytocin plays a major role in initiating labor in mammals, inparticular in humans. Thereby, it is assumed that oxytocin exerts saideffect in a direct as well as an indirect way, by contracting theuterine myometrium and by enhancing the synthesis and release ofcontractile prostaglandins from the uterine endometrium/decidua. Theseprostaglandins may furthermore play a role in the cervical ripeningprocess. This “up-regulation” of oxytocin receptors and increaseduterine sensitivity seems to be due to trophic effects of rising plasmalevels of estrogen towards term. By down-regulating oxytocin, it isexpected that both the direct (contractile) and indirect (increasedprostaglandin synthesis) effects of oxytocin on the uterus could beblocked. An oxytocin modulator, e.g. blocker or antagonist would likelybe efficacious for treating preterm labor.

A further condition related to oxytocin is dysmenorrhea, which ischaracterised by pain or discomfort associated with menses. The pain isbelieved to result from uterine contractions and ischemia, probablymediated by the effect of prostaglandins produced in the secretoryendometrium By blocking both the indirect and direct effects of oxytocinon the uterus, an oxytocin antagonist would be a likely candidate fortreating dysmenorrhea.

Some agents counteracting the action of oxytocin are currently used inclinical studies (6). Such tocolytic agents (i.e. uterine-relaxinagents) include beta-2-adrenergic agonists, magnesium sulfate andethanol. The leading beta-2-adrenergic agonist is Ritodrine, whichcauses a number of cardiovascular and metabolic side effects, includingtachycardia, increased renin secretion, hyperglycemia and reactivehypoglycemia in the infant. Further beta-2-adrenergic agonists,including terbutaline and albuterol have side effects similar to thoseof ritodrine. Magnesium sulfate at plasma concentrations above thetherapeutic range of 4 to 8 mg/dL can cause inhibition of cardiacconduction and neuromuscular transmission, respiratory depression andcardiac arrest, thus making this agent unsuitable when renal function isimpaired. Ethanol is as effective as ritodrine in preventing prematurelabor, but it does not produce a corresponding reduction in theincidence of fetal respiratory distress that administration of ritodrinedoes.

Atosiban, a peptide OT antagonist, suffers the problem of most peptides:low oral bioavailability resulting from intestinal degradation. Suchcompounds must be administered parenterally.

The development of non-peptide ligands for peptide hormone receptors isexpected to overcome this problem. Small molecule selective oxytocinantagonists have been reported by Merck. In addition to cyclichexapeptides, Merck suggested indanylpiperidines and tolyl-piperazinesas orally deliverable OT antagonists (7). In WO 96/22775 and U.S. Pat.No. 5,756,497, Merck reported benzoxazinylpiperidines or benzoxazinonesas OT receptor antagonists.

Specific sulfonamides have been reported to antagonize ocytocin at theocytocin receptor. Elf Sanofi's EP-A-0469984 and EP-A-0526348 reportN-sulfonyl indolines acting as antagonists of the vasopressin and theoxytocin receptors.

SUMMARY OF THE INVENTION

It is an object of the present invention to provide substances which aresuitable for the treatment of a variety of diseases, in particularpreterm labor, premature birth, dysmenorrhea, inappropriate secretion ofvasopressin, congestive heart failure, arterial hypertension, livercirrhosis, nephrotic syndrome and ocular hypertension.

It is notably an object of the present invention to provide chemicalcompounds which are able to down-regulate, including to antagonize, thefunction of OT and/or V1a in disease states in animals, preferablymammals, especially in humans.

It is also an object of the present invention to provide small moleculechemical compounds for the modulation, preferably the down-regulation orantagonization of the oxytocin receptor.

Moreover, it is an object of the present invention to provide methodsfor preparing said small molecule chemical compounds. It is furthermorean object of the present invention to provide a new category ofpharmaceutical formulations for the treatment of preterm labor anddysmenorrhea, and/or diseases mediated by the oxytocin receptor.

It is finally an object of the present invention to provide a method forthe treatment and/or prevention of disorders mediated by the oxytocinreceptor, like preterm labor, inappropriate secretion of vasopressin,congestive heart failure, arterial hypertension, liver cirrhosis,nephrotic syndrome, dysmenorrhea and ocular hypertension with oxytocinand/or vasopressin antagonists, acting for example by antagonizing thebinding of oxytocin and/or vasopressin to their receptor.

In a first aspect, the invention provides compounds of formula I:

wherein:

-   R¹ and R² are independently selected from the group consisting of H,    C₁-C₆-alkyl, aryl C₁-C₆-alkyl, heteroarylC₁-C₆-alkyl,    C₃-C₆-cycloalkyl C₁-C₆-alkyl and heterocycloalkyl C₁-C₆-alkyl; or-   R¹ and R², together with the nitrogen atom they are linked to, form    a substituted or unsubstituted 5-8-membered saturated, partially    unsaturated or aromatic ring containing optionally one or more    additional heteroatoms selected from O, N, S;-   A is selected from the group consisting of C(O) and SO₂;-   R³ is selected from a the group consisting of H, C₁-C₆-aklyl, aryl    C₁-C₆-alkyl, heteroaryl C₁-C₆-alkyl, aryl, heteroaryl,    C₃-C₆cycloalkyl C₁-C₆-alkyl, heterocycloalkyl C₁-C₆-alkyl,    C₂-C₆-alkenyl;-   B is selected from the group consisting of S, O and NR⁵;-   R⁴ and R⁵ are independently selected from the group consisting of H,    C₁-C₆-alkyl, aryl C₁-C₆-alkyl, heteroaryl C₁-C₆-alkyl, acyl, aryl    acyl, heteroaryl acyl C₃-C₆-cycloalkyl C₁-C₆-alkyl, heterocycloalkyl    C₁-C₆-alkyl, C₂-C₆-alkenyl; and-   n is an integer from 2 to 10;

In a second aspect, the invention provides a compound according toformula I for the treatment of disease.

In a third aspect, the invention provides a compound of formula L forthe preparation of a pharmaceutical composition.

In a fourth aspect, the invention provides a compound according toformula I for the modulation of the function of OT and/or V1a receptors.

In a fifth aspect, the invention provides a method of synthesis of acompound according to formula I.

DETAILED DESCRIPTION OF THE INVENTION

The following paragraphs provide definitions of the various chemicalmoieties that make up the compounds according to the invention and areintended to apply uniformly throughout the specification and claimsunless an otherwise expressly set out definition provides a broaderdefinition.

“C₁-C₆-alkyl” refers to monovalent alkyl groups having 1 to 6 carbonatoms. This term is exemplified by groups such as methyl, ethyl,n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-hexyl and thelike.

“C₃-C₆-cycloalkyl” refers to saturated or partially unsaturatedcarbocyclic rings having 3 to 6 carbon atoms. Examples includecyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohexenyl and thelike.

“C₃-C₆-heterocycloalkyl” refers to saturated or partially unsaturatedrings having 3 to 6 atoms and containing at least one heterotom selectedfrom N, S and O. Examples include pyrrolidinyl, piperidinyl,piperazinyl, imidazolidinyl, morpholinyl and the like.

“C₃-C₆cycloalkyl C₁-C₆-alkyl” refers to C₁-C₆-alkyl groups having anC₃-C₆-cycloalkyl substituent, such as, for example methyl-cyclopropane,ethyl-cyclohexane and the like.

“C₃-C₆-heterocycloalkyl C₁-C₆-alkyl” refers to C₁-C₆-alkyl groups havingan C₃-C₆-heterocycloalkyl substituent, such as, for examplemethyl-pyrrolidine, methyl piperidine, ethyl-tetrahydro-furan and thelike.

“Aryl” refers to an unsaturated aromatic carbocyclic group of from 6 to14 carbon atoms having a single ring (e.g. phenyl) or multiple condensedrings (e.g. naphthyl). Examples of aryl include phenyl, naphthyl,phenanthrenyl and the like.

“aryl C₁-C₆-alkyl” refers to C₁-C₆-alkyl groups having an arylsubstituent, such as, for example, benzyl, phenethyl and the like.

“Heteroaryl” refers to a monocyclic heteromatic, or a bicyclic or atricyclic fused-ring heteroaromatic group. Particular examples ofheteroaromatic groups include optionally substituted pyridyl, pyrrolyl,furyl, thienyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl,isothiazolyl, pyrazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl,1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl 1,2,5-oxadiazolyl,1,3,4-oxadiazolyl, 1,3,4-triazinyl, 1,2,3-triazinyl, benzofuryl,[2,3-dihydro]benzofuryl, isobenzofuryl, benzothienyl, benzotriazolyl,isobenzothienyl, indolyl, isoindolyl, 3H-indolyl, benzimidazolyl,imidazo[1,2-a]pyridyl, benzothiazolyl, benzoxazolyl, quinolizinyl,quinazolinyl, pthalazinyl, quinoxalinyl, cinnnolinyl, napthyridinyl,pyrido[3,4-b]pyridyl, pyrido[3,2-b]pyridyl, pyrido[4,3-b]pyridyl,quinolyl, isoquinolyl, tetrazolyl, 5,6,7,8-tetrahydroquinolyl,5,6,7,8-tetrahydroisoquinolyl, purinyl, pteridinyl, carbazolyl,xanthenyl or benzoquinolyl and the like.

“heteroaryl C₁-C₆-alkyl” refers to C₁-C₆-alkyl groups having aheteroaryl substituent, such as, for example, 2-furylmethyl,2-thienylmethyl, 2-(1H-indol-3-yl)ethyl and the like.

“Alkenyl” refers to alkenyl groups preferably having from 2 to 6 carbonatoms and having one or more sites of alkenyl unsaturation. Example ofalkenyl groups include ethenyl (—CH═CH₂), n-2-propenyl (allyl,—CH₂CH═CH₂) and the like.

“Alkynyl” refers to alkynyl groups preferably having from 2 to 6 carbonatoms and having one or more sites of alkynyl unsaturation. Examples ofalkynyl groups include ethynyl (—C≡CH), propargyl (—CH₂C≡CH), and thelike.

“Acyl” refers to the group (O)R where R includes “C₁-C₆-alkyl”, “aryl”,“heteroaryl”, “C₁-C₆-alkyl aryl” or “C₁-C₆-alkyl heteroaryl”.

“Acyloxy” refers to the group —OC(O)R where R includes “C₁-C₆-alkyl”,“aryl”, “heteroaryl”, “C₁-C₆-alkyl aryl” or “C₁-C₆-alkyl heteroaryl”.

“Alkoxy” refers to the group —R where R includes “C₁-C₆-alkyl” or “aryl”or “heteroaryl” or “C₁-C₆-alkyl aryl” or “C₁-C₆-alkyl heteroaryl”.Examples of alkoxy groups include by way of example, methoxy, ethoxy,phenoxy and the like.

“Alkoxycarbonyl” refers to the group —O—R where R includes “C₁-C₆-alkyl”or “aryl” or “heteroaryl” or “C₁-C₆-alkyl aryl” or “C₁-C₆-alkylheteroaryl”.

“Aminocarbonyl” refers to the group —C(O)NRR′ where each R, R′ includesindependently hydrogen or C₁-C₆-alkyl or aryl or heteroaryl or“C₁-C₆-alkyl aryl” or “C₁-C₆-alkyl heteroaryl”.

“Acylamino” refers to the group —NR(CO)R′ where each R, R′ isindependently hydrogen or “C₁-C₆-alkyl” or “aryl” or “heteroaryl” or“C₁-C₆-alkyl aryl” or “C₁-C₆-alkyl heteroaryl”.

“Halogen” refers to fluoro, chloro, bromo and iodo atoms.

“Sulfonyl” refers to a group “—SO₂—R” wherein R is selected from H,“C₁-C₆-alkyl”, “C₁-C₆-alkyl” optionally substituted with halogens, suchas, for example, an —SO₂—CF₃ group, e“aryl”, “heteroaryl”, “C₁-C₆-alkylaryl” or “C₁-C₆-alkyl heteroaryl”.

“Sulfoxy” refers to a group “—S(O)—R” wherein R is selected from H,“C₁-C₆-alkyl”, “C₁-C₆-alkyl” optionally substituted with halogens, suchas, for example, an —SO—CF₃ group, “aryl”, “heteroaryl”, “C₁-C₆-alkylaryl” or “C₁-C₆-alkyl heteroaryl”.

“Thioalkoxy” refers to groups —S—R where R includes “C₁-C₆-alkyl” or“aryl” or “heteroaryl” or “C₁-C₆-alkyl aryl” or “C₁-C₆-alkylheteroaryl”. Examples of thioalkoxy groups include thiomethoxy,thioethoxy, and the like.

“Substituted or unsubstituted”: Unless otherwise constrained by thedefinition of the individual substituent, the above set out groups, like“alkyl”, “alkenyl”, “alkynyl”, “aryl” and “heteroaryl” etc. groups canoptionally be substituted with from 1 to 5 substituents selected fromthe group consisting of “C₁-C₆-alkyl”, “C₁-C₆-alkyl aryl”, “C₁-C₆-alkylheteroaryl”, “C₂-C₆-alkenyl”, “C₂-C₆-alkynyl”, primary, secondary ortertiary amino groups or quarternary ammonium moieties, “acyl”,“acyloxy”, “acylamino”, “aminocarbonyl”, “alkoxycarbonyl”, “aryl”,“heteroaryl”, carboxyl, cyano, halogen, hydroxy, mercapto, nitro,sulfoxy, sulfonyl, alkoxy, thioalkoxy, trihalomethyl and the like.Within the framework of this invention, said “substitution” is meant toalso comprise situations where neighboring substituents undergo ringclosure, in particular when vicinal functional substituents areinvolved, thus forming e.g. lactams, lactones, cyclic anhydrides, butalso acetals, thioacetals, aminals formed by ring closure for instancein an effort to obtain a protective group.

“Pharmaceutically acceptable salts or complexes” refers to salts orcomplexes of the identified compounds of Formula I that retain thedesired biological activity and are not toxic. Examples of such saltsinclude, but are not restricted to, acid addition salts formed withinorganic acids (e.g. hydrochloric acid, hydrobromic acid, sulfuricacid, phosphoric acid, nitric acid, and the like), and salts formed withorganic acids such as acetic acid, oxalic acid, tartaric acid, succinicacid, malic acid, fumaric acid, maleic acid, ascorbic acid, benzoicacid, tannic acid, pamoic acid, alginic acid, polyglutamic acid,naphthalene sulfonic acid, naphthalene disul-fonic acid, andpoly-galacturonic acid. Said compounds can also be administered aspharmaceutically acceptable quaternary salts known by a person skilledin the art, which specifically include the quaternary ammonium salt ofthe Formula —NR,R′,R″⁺Z⁻, wherein R, R′, R″ is independently hydrogen,alkyl, or benzyl, and Z is a counterion, including chloride, bromide,iodide, —O-alkyl, toluenesulfonate, methylsulfonate, sulfonate,phos-phate, or carboxylate (such as benzoate, succinate, acetate,glycolate, maleate, malate, sate, citrate, tartrate, ascorbate,cinnamoate, mandeloate, and diphenylacetate).

“Pharmaceutically active derivative” refers to any compound that uponadministration to the recipient, is capable of providing directly orindirectly, the activity disclosed herein.

“Enantiomeric excess” (ee) refers-to the products that are obtained byan asymmetric synthesis, i.e. a synthesis involving non-racemic startingmaterials and/or reagents or a synthesis comprising at least oneenantioselective step, whereby a surplus of one enantiomer in the orderof at least about 52% ee is yielded. In the absence of an asymmetricsynthesis, racemic products are usually obtained that do however alsohave an activity as OT-R antagonists.

The term “preterm labor” or the term “premature labor” shall meanexpulsion from the uterus of an infant before the normal end ofgestation, or more particularly, onset of labor with effacement anddilation of the cervix before the 37^(th) week of gestation. It may ormay not be associated with vaginal bleeding or rupture of the membranes.

The term “dysmenorrhea” shall mean painful menstruation.

The term “caesarean delivery” shall mean incision through the abdominaland uterine walls for delivery of a foetus.

The present invention also includes the geometrical isomers, the opticalactive forms, enantiomers, diastereomers of compounds according toformula L mixtures of these, as well as their racemates and alsopharmaceutically acceptable salts.

Preferred R¹ and R² in compounds according to formula I are those thatare independently selected from the group consisting of H, methyl,ethyl, propyl and butyl, optionally substituted by substituted orunsubstituted C₁-C₆-alkoxy, preferably methoxy, substituted orunsubstituted C₂-C₆-alkenyl, preferably ethenyl, substituted orunsubstituted aryl or heteroaryl, preferably mono- or poly-halogensubstituted phenyl, methoxyphenyl, pyrrolidinone, furanyl,benzodioxolyl, substituted or unsubstituted C₃-C₆-cycloalkyl or5-6-membered heterocycle, preferably cyclopropyl, tetahydrofuryl andpyrrolidinone.

Preferred R³ in compounds according to formula I are those that areindependently selected from the group consisting of H, methyl, ethyl,propyl, butyl optionally substituted by substituted or unsubstitutedC₁-C₆-alkoxy, preferably methoxy, substituted or unsubstitutedC₂-C₆-alkenyl, preferably ethenyl, substituted or unsubstituted aryl orheteroaryl, preferably mono- or poly-halogen substituted phenyl,methoxyphenyl, pyrrolidinone, furanyl, benzodioxolyl, substituted orunsubstituted C₃-C₆-cycloalkyl or 5-6-membered heterocycle, preferablycyclopropyl, tetahydrofuryl and pyrrolidinone and aryl, optionallysubstituted by substituted or unsubstituted C₁-C₆-alkyl, preferablymethyl, halogen, substituted or unsubstituted C₁-C₆-alkoxy, preferablymethoxy.

Preferred R⁴ and R⁵ in compounds according to formula I are those thatare independently selected from the group consisting of H, methyl,ethyl, propyl and butyl, optionally substituted by substituted orunsubstituted C₁-C₆-alkoxy, preferably methoxyphenyl, substituted orunsubstituted C₂-C₆-alkenyl, preferably ethenyl, ethenylphenyl,substituted or unsubstituted acyl aryl, preferably, carbonyl aryl,substituted or unsubstituted aryl or heteroaryl, preferably mono- orpoly-halogen substituted phenyl, cyanophenyl, methylphenyl,tri-halo-methylphenyl, substituted or unsubstituted C₃-C₆-cycloalkyl or5-6-membered heterocycle, preferably cyclohexyl.

A particularly preferred embodiment of the present invention is atriazole derivative according to formula I wherein A is C(O), B is S andn is 2, 3 or 4.

Compounds of formula I may be used for the treatment of a disease.

Specifically, the compounds of formula I are suitable for use intreating disorders such as preterm labor, premature birth, dysmenorrhea,inappropriate secretion of vasopressin, congestive heart failure,arterial hypertension, liver cirrhosis, nephrotic syndrome, ocularhypertension and for stopping labor prior to cesarean delivery. Thecompounds of the present invention are in particular useful for thetreatment of preterm labor, premature birth and dysmenorrhea.

Preferably, the compounds according to Formula I alone or in a form of apharmaceutical composition are suitable for the modulation of oxytocinand/or vasopressin (in particular V_(1a)) function(s), thus specificallyallowing the treatment and/or prevention of disorders which are mediatedby the oxytocin and/or vasopressin receptors. Such modulation preferablyinvolves the inhibition of OT-R function(s), notably by theantagonization of the oxytocin receptor in mammals, and in particular inhumans.

Abnormal activity or hyperactivity of the oxytocin and/or vasopressinreceptors are frequently involved in various disorders including theabove enumerated disorders and disease states. Hence, the compoundsaccording to the invention may be used for the treatment of disorders bymodulating OT-R function or pathways. The modulation of the OT-Rfunction or pathways may involve the down-regulation and/or inhibitionof the oxytocin receptor. The compounds of the invention may be employedalone or in combination with further pharmaceutical agents, e.g. with afurther OT-R modulator.

When employed as pharmaceuticals, the triazole derivatives of thepresent invention are typically administered in the form of apharmaceutical composition. Hence, pharmaceutical compositionscomprising a compound of Formula I and a pharmaceutically acceptablecarrier, diluent or excipient are also within the scope of the presentinvention. A person skilled in the art is aware of a whole variety ofsuch carriers, diluents or excipients suitable to formulate apharmaceutical composition.

The compounds of the invention, together with a conventionally employedadjuvant, carrier, diluent or excipient may be formulated aspharmaceutical compositions and unit dosages thereof, and in such formmay be employed as solids, such as tablets or filled capsules, orliquids such as solutions, suspensions, emulsions, elixir, or capsulesfilled with the same, all for oral use, or in the form of sterileinjectable solutions for parenteral (including subcutaneous) use. Suchpharmaceutical compositions and unit dosage forms thereof may compriseingredients in conventional proportions, with or without additionalactive compounds or principles, and such unit dosage forms may containany suitable effective amount of the active ingredient commensurate withthe intended daily dosage range to be employed.

When employed as pharmaceuticals, the triazole derivatives of thisinvention are typically administered in the form of a pharmaceuticalcomposition. Such compositions can be prepared in a manner well known inthe pharmaceutical art and comprise at least one active compound.Generally, the compounds of this invention are administered in apharmaceutically effective amount. The amount of the compound actuallyadministered will typically be determined by a physician, in the lightof the relevant circumstances, including the condition to be treated,the chosen route of administration, the actual compound administered,the age, weight, and response of the individual patient, the severity ofthe patient's symptoms, and the like.

The pharmaceutical compositions of the invention can be administered bya variety of routes including oral, rectal, transdermal, subcutaneous,intravenous, intramuscular, and intranasal. Depending on the intendedroute of delivery, the compounds are preferably Formulated as eitherinjectable or oral compositions. The compositions for oraladministration can take the form of bulk liquid solutions orsuspensions, or bulk powders. More commonly, however, the compositionsare presented in unit dosage forms to facilitate accurate dosing. Theterm “unit dosage forms” refers to physically discrete units suitable asunitary dosages for human subjects and other mammals, each unitcontaining a predetermined quantity of active material calculated toproduce the desired therapeutic effect, in association with a suitablepharmaceutical excipient. Typical unit dosage forms include prefilled,premeasured ampoules or syringes of the liquid compositions or pills,tablets, capsules or the like in the case of solid compositions. In suchcompositions, the triazole compound is usually a minor component (fromabout 0.1 to about 50% by weight or preferably from about 1 to about 40%by weight) with the remainder being various vehicles or carriers andprocessing aids helpful for forming the desired dosing form.

Liquid forms suitable for oral administration may include a suitableaqueous or nonaqueous vehicle with buffers, suspending and dispensingagents, colorants, flavors and the like. Solid forms may include, forexample, any of the following ingredients, or compounds of a similarnature: a binder such as microcrystalline cellulose, gum tragacanth orgelatine; an excipient such as starch or lactose, a disintegrating agentsuch as alginic acid, Primogel, or corn starch; a lubricant such asmagnesium stearate; a glidant such as colloidal silicon dioxide; asweetening agent such as sucrose or saccharin; or a flavoring agent suchas peppermint; methyl salicylate, or orange flavoring.

Injectable compositions are typically based upon injectable sterilesaline or phosphate-buffered saline or other injectable carriers knownin the art. As above mentioned, the triazole derivatives of Formula I insuch compositions is typically a minor component, frequently rangingbetween 0.05 to 10% by weight with the remainder being the injectablecarrier and the like.

The above described components for orally administered or injectablecompositions are merely representative. Further materials as well asprocessing techniques and the like are set out in Part 8 of in (8).

The compounds of this invention can also be administered in sustainedrelease forms or from sustained release drug delivery systems. Adescription of representative sustained release materials can also befound in the incorporated materials in (8).

Still a further object of the present invention is a process forpreparing preparing [1,2,4]triazole derivatives according to Formula I.

The triazole derivatives exemplified in this invention may be preparedfrom readily available or previously described starting materials usingthe following general methods and procedures. It will be appreciatedthat where typical or preferred experimental conditions (i.e. reactiontemperatures, time, moles of reagents, solvents, etc.) are given, otherexperimental conditions can also be used unless otherwise stated.Optimum reaction conditions may vary with the particular reactants orsolvents used, but such conditions can be determined by one skilled inthe art by routine optimisation procedures.

Synthesis of Compounds of the Invention:

Generally, the [1,2,4]triazole derivatives according to the generalFormula I may be obtained by several processes, using bothsolution-phase and solid-phase chemistry protocols. Depending on thenature of R¹-R⁴, A, B and n, certain processes will, in some instances,be preferred over others, and it is assumed that the choice of the mostsuitable process will be known to the practitioner skilled in the art.

Five examples of synthetic pathways for compounds of formula I will bedescribed.

The following abbreviations refer respectively to the definitions below:

-   ACN (Acetonitrile)-   AMEBA (Acid-sensitive Methoxy benzaldehyde)-   CDCl₃ (deuterated chloroform)-   cHex (Cyclohexanes)-   DCM (Dichloromethane)-   DECP (Diethylcyanophosphonate)-   DIC (Diisopropyl carbodiimide)-   DMAP (4-Dimethylaminopyridine)-   DMF (Dimethylform-amide)-   DMSO (Dimethylsulfoxide)-   DMSO-d₆ (deuterated dimethylsul-foxide)-   EDC (1-(3-Dimethyl-amino-propyl)-3-ethylcarbodiimide)-   EtOAc (Ethyl acetate)-   Et₂O (Diethyl ether)-   HOBt (1-Hydroxybenzotriazole)-   K₂CO₃ (potassium carbonate)-   NaH (Sodium hydride)-   NaHCO₃ (Sodium bicarbonate)-   nBuLi (n Butyllithium)-   TBTU    (O-Benzotriazolyl-N,N,N′,N′-tetramethyluronium-tetrafluoroborate)-   TEA (Triethyl amine)-   TFA (Trifluoro-acetic acid)-   THF (Tetrahydrofuran)-   MgSO₄ (Magnesium sulfate)-   PetEther (Petroleum ether)-   rt (room temperature).    Protocol I:

A preferred pathway for preparing [1,2,4]triazole derivatives accordingto the general Formula I, wherein B is a sulphur moiety (Formula Ia),with R¹, R², R³ and R⁴, A and n being defined as above, consists in thealkylation of the corresponding mercaptotriazole precursor of formula IIin presence of an appropriate alkylating agent R⁴X (formula m) in whichR⁴ is as defined above and X is a leaving group such as chloro, bromo,iodo, methanesulfonate or p-toluenesulfonate. This alkylation followssolution-phase chemistry protocols well known to those skilled in theart such as shown in Scheme I. The alkylation is conducted in any of avariety of solvents, including methanol, ethanol, 2-methoxyethanol,tetrahydrofuran, N,N-dimethylformamide, dichloromethane and water,depending on the properties of the particular substituents, in thepresence of a base, such as a trialkylamine, alkoxide or hydroxide. Thealkylation reaction is generally run at a temperature comprised between0° C. and 125° C., depending on the reactivity of the alkylating agent.

Mercaptotriazole derivatives of Formula II, used for the preparation oftriazoles derivatives of compounds of formula Ia according to scheme Ican be prepared from an appropriate amine IV, using a variety ofsynthetic strategies, of which some selected examples are shown inScheme II (9-14).

First, an amine of formula IV may be converted to a dithiocarbamateester of formula V in a one-pot two-step sequence involving treatmentwith carbon disulfide in the presence of a base such as triethylaminefollowed by alkylation with methyl iodide. Treatment of adithiocarbamate ester of formula V with hydrazine affords a4-substituted thiosemicarbazide of formula VI (scheme II).

Then, reaction of a thiosemicarbazide of formula VI with the appropriateacid chloride of formula VII leads to an acylthiosemicarbazide offormula VIII (scheme II).

Finally, mercaptotriazoles of formula II may be obtained either bydirect reaction of the thiosemicarbazide derivative of formula VI withan appropriate acid derivative of formula IX (for example reaction witha trimethyl orthoester at elevated temperature in a suitable solvent,such as 2-methoxyethanol at reflux) or by cylization of anacylthiosemicarbazide of formula VIII in presence of hydroxide oralkoxide (scheme II).

An alternative way of obtaining an acylthiosemicarbazide of formula VIIIis first reacting an amine of formula IV following standard reactionconditions widely described in the literature (9-14) to obtain anisothiocyanate of formula X which is then added to an acid hydrazide offormula XI to lead to an acylthiosemicarbazide of formula VIII (schemeII). Acid hydrazides of formula XI can be readily obtained from thecorresponding ester which is either commercial or can be prepared fromavailable starting materials according to standard protocols well knownto the practitioner skilled in the art.

Derivatives of mecaptotriazoles of formula II can be prepared usingknown modifications to the Scheme II reaction sequences.

Protocol II:

An another preferred pathway for preparing [1,2,4]triazole derivativesaccording to the general Formula I wherein, wherein B can be S (formulaIa), NR⁵ (formula Ib) or O (formula Ic), with R¹, R², R³, R⁴ and R⁵, Aand n being defined as above, consists in the displacement of a leavinggroup on the triazole, e.g. chlorotriazole of formula XII ormethanesulfonyltriazole of formula XIII. The leaving group on thetriazole can be displaced by an appropriate nucleophile of formularespectively XIV, XV or XVI under reaction conditions well known to theperson skilled in the art and as described in Scheme III.

For example, S-substituted mercaptotriazoles of formula Ia (generalFormula I, wherein B is a Sulphur moiety) can be prepared by addition ofa thiol R⁴SH (formula XIV), wherein R⁴ is defined as above, on achlorotriazole of formula XII or a methylsulfonyltriazole XIII in thepresence of a base such as N,N-diisopropylethylamine, at elevatedtemperature (for example, in DMF at reflux).

Aminotriazoles of formula Ib (general Formula I, wherein B is NR⁵) canbe obtained by heating a chlorotriazole of formula XIII or amethanesulfonyltriazole of formula XIII with an amine of formula R⁴R⁵NH(XV), where R⁴ and R⁵ are defined as above.

Alkoxy and aryloxytriazole of formula Ic (general Formula I, wherein Bis Oxygen) can be prepared by heating a chlorotriazole XII or amethanesulfonyltriazole XIII with the appropriate alkoxyde or phenoxideanion R₄O⁻ (formula XVI), where R₄ is defined as above.

The chlorotriazoles of formula XII used for the preparation of triazolesof formula Ia, Ib or Ic according to scheme III may be prepared bytreatment of a mercaptotriazole precursor of formula II with chlorineunder anhydrous conditions in a solvent such as chloroform ordichloromethane, as shown in Scheme IV.

The methylsulfonylthiotriazoles of formula XIII used for the preparationof triazoles of formula Ia, Ib or Ic according to scheme III may beprepared by alkylation of the same mercaptotriazole precursor of formulaII with methyl iodide to lead to a methylthiotriazole of formula XVIIwhich is then oxidized into the methylsulfunonyltriazole of formula XIIIusing hydrogen peroxide in acetic acid or similar methods known to theperson skilled in the art and as described in Scheme IV.

Mercaptotriazole derivatives of Formula II, used for the preparation ofchlorotriazoles of formula XII and methylsulfonylthiotriazoles offormula XIII according to scheme IV can be prepared from an appropriateamine IV, using a variety of synthetic strategies, of which someselected examples are previously shown in Scheme II (see protocol I).

Protocol III:

An another preferred pathway for preparing [1,2,4]triazole derivativesaccording to the formula Id (formula I wherein, wherein B is NR⁵ andR⁵=H) can be prepared following the synthetic route described in SchemeV.

An appropriate amine of formula IV is heated together with a S-methylthiosemicarbyzide derivative of formula XVIII to give an aminoguanidineof formula XIX. Heating an aminoguanidine of formula XIX with anappropriate carboxylic acid of formula XX provides an aminotriazole offormula Id. Aminoguanidines of formula XIX can be also obtained by anhydrazine treatment of isothioureas of formula XXI.

Protocol IV:

An another preferred pathway for the preparation of [1,2,4]triazolederivatives according to the formula Id (formula I wherein, wherein B isNR⁵ and R⁵=H) consists in the condensation of an aminotriazole ofstructure Ie (formula I wherein, wherein B is NR⁵ and R⁴=R⁵=H) with anaromatic aldehyde under suitable reaction conditions well known to theperson skilled in the art. Reduction of the resulting Schiff base offormula XXII with a suitable agent such as sodium borohydride leads the[1,2,4]triazole derivatives according to the formula Id (Scheme VI).

Aminotriazole of formula Ie used to prepare triazoles of formula Idaccording to the above scheme VI can be prepared by different syntheticroutes, including the one described in Scheme V, starting with thesuitable S-methyl thiosemicarbazide derivative XVIII with R⁴=H.

[1,2,4]Triazole derivatives according to the general Formula I, wherebythe substituents R¹-R⁴, A, B and n are as above defined, can be preparedusing modifications to Schemes I to VI reaction sequences or by othercurrent methods or procedures according to published literature wellknown to the practitioner skilled in the art (9-14).

Protocol V:

According to yet another preferred process, [1,2,4]triazole derivativesaccording to the general Formula I, whereby the substituents R¹, R², R³,R⁴ and R⁵, A, B and n are as above defined, are prepared by solid-phaseand/or mixed solid-/solution-phase synthesis protocols such as, e.g.,those described in the Example I and shown in Scheme VII.

It will be appreciated by the practitioner skilled in the art thatbasically the same conditions, methods and reagents as above describedin Schemes I to VI for the sollution-phase synthesis of compounds ofFormula I can be applied to the solid-phase and/or mixedsolid-/solution-phase synthesis of said compounds.

In the context of such a solid-phase and/or mixed solid-/solution-phasesynthesis protocol (Protocol V, Scheme VII), the R¹ or R²-groups ofcompounds II, VII-IX, XI-XIII, XVII, XX and XXII shown in Schemes I-VI,are found on a suitable resin comprising the appropriate cleavablelinker. The circles within the Scheme VII illustrate the resin beads towhich the corresponding compounds are linked during the solid phasesynthesis. It is to be understood that further to the mentioned resintypes, other suitable reagents, notably resins, known to a personskilled in the art, could be employed for the solid-phase synthesis ofcompounds of general Formula I.

Thus, in one preferred scenario, an amino-derivatised resin of formulaXXV is obtained by coupling of an appropriate amine of formula XXV witha suitable resin carrying an aldehyde moiety (e.g., AMEBA II (15) orArgoGel-CHO resin) of formula XXIII, using standard reductive aminationconditions well known to the practitioner skilled in the art (15).

According to the methods outlined in Scheme VII and describedhereinafter in the Examples I, this intermediate of formula XXV can thenbe reacted with an acyl or sulfonyl chloride of formula XXVI containingan ester moiety, in the presence of a base, (e.g.,N-ethyldiisopropylamine) to lead to a compound of formula XXVII.

Then, addition of an excess of hydrazine to a compound of formula XXVIIat 50° C. leads to the corresponding acid hydrazide of formula XXVIII.This acid hydrazide of formula XXVIII is then converted intosemicarbazide corresponding to a structure of formula XXX by addition ofa isothiocyanate of formula XXIX at room temperature.

The semicarbazide of formula XXX is then cyclised into a triazolederivative of formula XXXI under basic conditions (e.g., 0.3 M KOH), atelevated temperature, such as 65° C. The resulting cyclized derivativeof formula XXXI can be further functionalized in the presence of a base(e.g. N-ethyldiisopropylamine) by an appropriate alkylating agent R⁴X offormula IIII wherein R⁴ is defined as above and “X” is a leaving groupsuch as chloro, bromo, iodo, methanesulfonate or p-toluenesulfonate. Theresulting product of formula XXXII can be cleaved from the resin underacidic conditions (e.g. in a TFA/DCM solution), affording thecorresponding [1,2,4]triazole of formula Ia (formula I wherein B is aSulphur moiety) as described hereinafter in the Example I.

Amines of formula XV used according to scheme VII are either commercial,e.g., 1-(3-amino-propyl)-pyrrolidin-2-one, cyclopropyl-methylamine,phenethylamine, furan-2-yl-methylamine, 2-methoxy-ethylamine,butylamine, 3-methoxy-propylamine, benzo[1,3]dioxol-5-yl-methylamine,propylamine, 4-fluoro-benzylamine, (tetrahydrofuran-2-yl)-methylamine,2-methoxy-benzylamine, 4-methoxy-benzylamine, benzylamine,isobutylamine, allylamine, or can be prepared from readily availablestarting material according published literature procedures and methodswell known to the practioner skilled in the art.

Compounds of formula XXVI may also be either commercial, e.g., methyl3-(chloroformyl)-propionate, methyl 4-(chloroformyl)-butyrate, methyl5-(chloroformyl)-pentanoate, or can be prepared from readily availablestarting material according published literature procedures and currentmethods well known to the practioner skilled in the art.

Isothiocyanates of formula XXI are either commercial, e.g.,1-isothiocyanato-3-methyl-benzene, 1-chloro-4-isothiocyanato-benzene,1-isothiocyanato-4-methyl-benzene,2-isothiocyanatomethyl-tetrahydro-furan,(2-isothiocyanato-ethyl)-benzene,1-isothiocyanato-methyl-4-methyl-benzene, 3-isothiocyanato-propene,isothiocyanato-methane, 1-isothiocyanato-2-methyl-propane,1-fluoro-4-isothiocyanato-benzene, isothio-cyanato-methyl-benzene,isothiocyanato-benzene, 1-chloro-3-isothiocyanato-benzene,1-isothio-cyanato-3-methoxy-propane, 1-isothiocyanato-3-methoxy-benzene,or can be prepared from readily available starting material accordingpublished literature procedures and methods well known to the practionerskilled in the art.

Alkylating agent R⁴X of formula III are either commercial, e.g.,benzylbromide, (3-bromo-propenyl)-benzene, allylbromide,bromomethyl-cyclohexane, 1-bromomethyl-3-methyl-benzene,1-bromomethyl-4-fluoro-benzene, 1-bromomethyl-3,5-dimethyl-benzene,1-bromomethyl-3-fluoro-benzene, 1-bromomethyl-4-trifluoromethyl-benzene,(2-bromo-ethoxy)-benzene, bromoethane, 1-bromo-2-methoxy-ethane,1-bromomethyl-4-methyl-benzene, 2-bromomethyl-tetrahydro-pyran,2-bromo-1-phenyl-ethanone, bromo-acetic acid ethyl ester,1-bromomethyl-2,3,4,5,6-pentafluoro-benzene, (2-bromo-ethyl)-benzene,1-bromomethyl-2-methyl-benzene, 1-bromomethyl-2-fluoro-benzene,1-bromomethyl-3-chloro-benzene, 1-bromomethyl-2-chloro-4-fluoro-benzene,3-bromomethyl-benzonitile, 1-bromo-butane, or can be prepared fromreadily available starting material according published literatureprocedures and current methods well known to the practioner skilled inthe art.

The reaction sequences outlined in the above Schemes (I to VI) provideenantiomerically pure compounds of general Formula I, ifenantiomerically pure starting materials are used. (R) as well as (S)enantiomers can be obtained depending upon whether (R) or (S) forms ofcommercially available starting materials are used.

According to a further general process, compounds of Formula I can beconverted to alternative compounds of Formula I, employing suitableinterconversion techniques.

If the above set out general synthetic methods are not applicable forobtaining compounds according to Formula I and/or necessaryintermediates for the synthesis of compounds of Formula I, suitablemethods of preparation known by a person skilled on the art should beused. In general, the synthesis pathways for any individual compound ofFormula I will depend on the specific substitutents of each molecule andupon the ready availability of intermediates necessary; again suchfactors being appreciated by those of ordinary skill in the art. For allthe protection, de-protection methods, see (16) and (17).

Compounds of this invention can be isolated in association with solventmolecules by crystallization. The pharmaceutically acceptable acidaddition salts of the compounds of Formula I, which contain a basiccenter, may be prepared in a conventional manner. For example, asolution of the free base may be treated with a suitable acid, eitherneat or in a suitable solution, and the resulting salt isolated eitherby filtration or by evaporation under vacuum of the reaction solvent.Pharmaceutically acceptable base addition salts may be obtained in ananalogous manner by treating a solution of compound of Formula I with asuitable base. Both types of salt may be formed or interconverted usingion-exchange resin techniques.

EXAMPLES

The invention will be illustrated by means of the following exampleswhich are not to be construed as limiting the scope of the invention.

The compounds of the present invention may be synthesized according tothe different synthesis pathways provided above. The following examplesillustrate preferred methods for synthesizing the compounds according toformula I and determining their activities.

Example 13-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide(1) (Compound of Formula Ia) See Protocol V, Scheme VII

Protocol V:Step 1: Reductive Amination (Compound of Formula XXV):

In a round bottomed flask, fitted with stirrer and nitrogen inlet, wassuspended AMEBA II (15) resin of formula XXIII (50 g, 0.048 mol, 0.96mmol/g), in mixture 9:1 of THF/TMOF (500 mL). Primary amine (compound offormula XXIV), e.g. 2-methyoxy benzylamine (0.072 mol, 7.9 mL, 1.5 eq),followed by acetic acid (2.75 mL, 1.5 eq) were sequentially added. Theresulting mixture was stirred for 1 hour (imine formation). Sodiumtriacetoxyborohydride (15.25 g, 0.072 mol, 1.5 eq) was added to theflask and the reaction stirred overnight at room temperature undernitrogen. The excess of hydride was neutralized with a 2 N NaOH solution(20 mL). The resin was recovered on a sintered funnel and was washedsequentially with DMF (250 mL), water (250 mL), DMF (250 mL), water (250mL), acetone (250 mL), methanol (250 mL), acetone (250 mL) and methanol(250 nm). The resin was first dried by flusing air for 1 hour, then invacuo at 60° C.

Step 2: Reaction of the Resin with an Acylor Sulfonyl Chloride (Compoundof Formula XXVII

The resulting Amino-derivatised AMEBA II resin of formula XXV obtainedfrom Step 1 (0.75 mmol/g of resin), was suspended in dichloromethane (10mL/g of resin) in a round bottomed flask. An acid chloride or sulfonylchloride of formula XXVI (3 eq), e.g. methyl3-(chloroformyl)-propionate, was added, followed byN-ethyldiisopropylamine (3 eq). The reaction mixture was shaken at roomtemperature for 18 hours. The resin was filtered and washed sequentiallywith DCM, DMF, DCM and MeOH before being dried in vacuo.

Step 3: Hydrazine Addition (Compound of Formula XXVIII):

Ester derivatised AMEBA II resin of formula XXVII obtained from Step 2(˜0.7 mmol/g), was put into a round bottomed flask with a magneticstirrer. To the flask was added N,N-dimethylformamide (5 mL/g of resin),hydrazine hydrate (5 mL/g of resin). A water condenser was fitted andthe reaction was stirred slowly at 50° C. for 18 hours. The reaction wasallowed to cool to room temperature, filtered and the resin washed fivetimes with water and the waste disposed of accordingly. The resin wasthen washed sequentially with DMF, DCM and MeOH before being dried invacuo.

Step 4: Isocyanate Addition (Compound of Formula XXX):

The resin linked to the resulting acid hydrazide of formula XXVIII andrecovered from above Step 3 (1.5 g, ˜0.7 mmol/g), was weighed intoboiling tubes. Standard solutions of the isothiocyanates of formulaXXIX, e.g. 1-isothiocyanate-3-methoxy-benzene, were made up (0.42 M inanhydrous ml). These standard solutions (25 mL, 10.5 mmol, 10 eq) werethen added to the boiling tubes, which were sealed with a pressurereleasing septum. The tubes were shaken at room temperature for 66hours. The resin of each tube was filtered and washed with 2×DMF and thewaste disposed of accordingly. The resin was then washed sequentiallywith DCM and MeOH before being dried in vacuo.

Step 5: Cyclization (Compound of Formula XXXI):

The resins resulting from the previous Step 4 and of formula X, weretransferred to a clean boiling tube and a 3:2 mixture of 1,4-dioxane and0.3M KOH (20 mL) was added. The tubes were heated to 65° C. and shakenfor 18 hours. The reactions were allowed to cool to room temperature.The resin was washed with 3× water, 2×MeOH, 2×DCM and 2×MeOH beforebeing dried in vacuo.

Step 6: Alkylation (Compound of Formula XXXII:

The resin-bound compound of formula XXXI obtained from Step 5, wastransferred into a 96-well filter-plate (approximatively 50 mg of dryresin/well) and each well treated with 1 ml of alkyl bromide (formulaIII) solution (0.21 mmol/ml of 1,4-dioxane), e.g.1-Bromomethyl-3-chloro-benzene. N-ethyldiisoprpylamine (50 μl) was addedto each well, the plate sealed and shaken at room temperature for 18hours. The resin was filtered and washed with 2×DMF and the wastedisposed of accordingly. The resin was then washed sequentially withDMF, DCM, MeOH and finally DCM before being dried in vacuo.

Step 7: Cleavageform the Resin (Compound of Formula Ia):

A standard solution of 60% TFA/DCM was prepared. This solution (3×0.5ml) was dripped through each well of the filter plate containing theresin-bound compound of formula XXXII obtained from Step 6, collectingin a 2 ml plate. The solvents were evaporated. This procedure wasrepeated once (3×0.5 ml of 60% TFA/DCM solution) and the solvents wereremoved in vacuo. Dry THF (0.5 mL) and MeOH (0.5 mL) were finallydripped through and the solvent removed in vacuo. The final compound(formula Ia) obtained after purification by two successive flashchromatography processes (first column using 100% ethyl acetateprogressing to 5% methanol/ethyl acetate as eluent; second columnperformed with a mixture 50% hexane/ethyl acetate progressing to 100%ethyl acetate over 1 hour as eluent) is3-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-methoxyphenyl)-4H1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide (1) (¹H NMR (400 MHz,CDCl₃): 2.5 (m, 2H), 2.6 (m, 2H), 3.6 (s, 3H), 3.7 (s, 3H), 4.1-4.3 (m,4H), 5.3 (m, 1H), 5.4 (m, 2H), 5.7 (m, 2H), 5.8 (m, 1H), 6.9-7.1 (m,6H), 7.2 (m, 1H). M⁺(ESI⁺): 523).

The below listed compounds in Table 2 (designated by example numbers)were prepared in a similar way by following the general method asoutlined in Example 1 and using the corresponding starting amines (Table1).

TABLE 1 Chemical Structure FMWT

142.20

71.12

121.18

97.12

75.11

73.14

89.14

151.17

59.11

125.15

101.15

137.18

137.18

107.16

73.14

57.10

TABLE 2 Example No. Chemical Structure M.W. IUPAC-Name M⁺(ESI⁺) 2

507.062-{4-benzyl-5-[(3-chlorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-methylbenzyl)propanamide507 3

507.063-{4-(3-chlorophenyl)-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)propanamide507 4

489.043-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-methoxypropyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide489 5

490.603-[5-[(3-fluorobenzyl)sulfanyl]-4-(4-methylphenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide491 6

500.66N-(2-methoxybenzyl)-3-{4-(4-methylbenzyl)-5-[3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}propanamide501 7

456.583-{5-[(3-fluorobenzyl)sulfanyl]-4-isobutyl-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)propanamide457 8

507.063-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-methylphenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide507 9

472.613-[5-(benzylsulfanyl)-4-(4-methylphenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide473 10

438.593-[5-(benzylsulfanyl)-4-isobutyl-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide439 11

511.023-{4-(3-chlorophenyl)-5-[(4-fluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl)-N-(2-methoxybenzyl)propanamide511 12

493.033-[5-(benzylsulfanyl)-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide493 13

452.623-{4-isobutyl-5-[(3-methylbenzyl)sulfanyl}-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)propanamide453 14

480.63N-(2-methoxybenzyl)-3-[5-[(3-methylbenzyl)sulfanyl]-4-(tetrahydro-2-furanylmethyl)-4H-1,2,4-triazol-3-yl]propanamide481 15

463.43N-butyl-3-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]propanamide463 16

502.64N-(2-methoxybenzyl)-3-{4-(3-methoxyphenyl)-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}propanamide503 17

430.963-{5-[(3-chlorobenzyl)sulfanyl]-4-methyl-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)propanamide431 18

484.593-[5-[(3-fluorobenzyl)sulfanyl]-4-(tetrahydro-2-furanylmethyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide485 19

436.583-{4-allyl-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)propanamide437 20

506.603-[5-[(3-fluorobenzyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide507 21

420.583-[5-(butylsulfanyl)-4-(3-methoxypropyl)-4H-1,2,4-triazol-3-yl]-N-(4-methoxybenzyl)propanamide421 22

454.59N-benzyl-3-{4-(3-methoxypropyl)-5-[(2-phenoxyethyl)sulfanyl]-4H-1,2,4-triazol-3-yl}propanamide455 23

490.603-{4-benzyl-5-[(2-fluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl)-N-(2-methoxybenzyl)propanamide491 24

511.023-[5-[(3-chlorobenzyl)sulfanyl]-4-(4-fluorophenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide511 25

476.573-[5-(benzylsulfanyl}-4-(4-fluorophenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide477 26

461.413-[5-[(3-chlorophenyl)-4H-1,2,4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-(cyclopropylmethyl)propanamide461 27

513.623-[5-[(3-cyanobenzyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide514 28

466.603-[5-(benzylsulfanyl)-4-(tetrahydro-2-furanylmethyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide467 29

468.62N-(2-methoxybenzyl)-3-{4-(3-methoxypropyl)-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}propanamide469 30

422.553-[4-allyl-5-(benzylsulfanyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide423 31

472.583-[5-[(3-fluorobenzyl)sulfanyl]-4-(3-methoxypropyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide473 32

490.603-{4-(4-fluorophenyl)-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)propanamide491 33

454.593-[5-(benzylsulfanyl)-4-(3-methoxypropyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide455 34

494.573-[5-[(3-fluorobenzyl)sulfanyl]-4-(4-fluorophenyl}-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide495 35

440.543-{4-allyl-5-[(3-fluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)propanamide441 36

521.083-{4-(3-chlorophenyl)-5-[(3,5-dimethylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)propanamide521 37

446.983-{4-(3-chlorophenyl)-5-[(3-fluorobenzyl)sulfanyl)-4H-1,2,4-triazol-3-yl}-N-isobutylpropanamide447 38

516.663-[5-[(3,5-dimethylbenzyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide517 39

470.953-{5-[(2-chloro-4-fluorobenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}-N-(2-furylmethyl)propanamide471 40

504.633-[5-[(3-fluorobenzyl)sulfanyl]4-(4-methylbenzyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide505 41

428.993-{4-(3-chlorophenyl)-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-propylpropanamide429 42

465.403-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxyethyl)propanamide465 43

436.583-[5-(allylsulfanyl)-4-(4-methylbenzyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide437 44

479.433-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-(3-methoxypropyl)propanamide479 45

443.013-{4-(3-chlorophenyl)-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-isobutylpropanamide443 46

486.64N-(2-methoxybenzyl)-3-[5-[(3-methylbenzyl)sulfanyl]-4-(4-methylphenyl)-4H-1,2,4-triazol-3-yl]propanamide487 47

506.603-[5-[(2-fluorobenzyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide507 48

486.643-[5-(benzylsulfanyl)-4-(4-methylbenzyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide487 49

486.643-{4-benzyl-5-[(3-methylbenzyl)sulfanyl)-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)propanamide487 50

441.00N-allyl-3-{4-(3-chlorophenyl)-5-[(3,5-dimethylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}propanamide441 51

490.603-[5-[(2-fluorobenzyl)sulfanyl]-4-(3-methylphenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide491 52

456.583-{5-[(4-fluorobenzyl)-sulfanyl]-4-isobutyl-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)propanamide457 53

452.623-[5-[3,5-dimethylbenzyl)-sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-isobutylpropanamide453 54

446.983-{4-(3-chlorophenyl)-5-[(4-fluorobenzyl)sulfanyl)-4H-1,2,4-triazol-3-yl}-N-isobutylpropanamide447 55

463.43N-butyl-3-[5-[(3-chlorobenzyl)sulfanyl]-4-(4-chlorophenyl)-4H-1,2,4-triazol-3-yl]propanamide463 56

511.473-[5-[(3-chlorobenzyl)-sulfanyl]-4-(4-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-(2-phenylethyl)propanamide511 57

472.583-[5-[(2-fluorobenzyl)-sulfanyl]-4-(3-methoxypropyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide473 58

471.023-{4-(3-chlorophenyl)-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(tetrahydro-2-furanylmethyl)propanamide471 59

491.063-{4-(4-chlorophenyl)-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-phenylethyl)propanamide491 60

502.043-{4-(3-chlorophenyl)-5-[(3-cyanobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-phenylethyl)propanamide502 61

564.55N-(4-fluorobenzyl)-3-[5-[(2,3,4,5,6-pentafluorobenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]propanamide565 62

440.543-{4-allyl-5-[(4-fluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)propanamide441 63

441.003-[5-[(3-chlorobenzyl)-sulfanyl]-4-(3-methylphenyl)-4H-1,2,4-triazol-3-yl]-N-(cyclopropylmethyl)propanamide441 64

485.053-[5-[(3-chlorobenzyl)sulfanyl]-4-(tetrahydro-2-furanylmethyl)-4H-1,2,4-triazol-3-yl]-N-(2-phenylethyl)propanamide485 65

488.613-[5-(benzylsulfanyl)-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide489 66

400.553-{4-allyl-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(tetrahydro-2-furanylmethyl)propanamide401 67

438.553-[5-(allylsulfanyl)-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide439 68

443.01N-butyl-3-(5-[(3-chlorobenzyl)sulfanyl]-4-(3-methylphenyl)-4H-1,2,4-triazol-3-yl]propanamide443 69

444.993-{4-(4-chlorophenyl)-5-[(4-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl)-N-(2-methoxyethyl)propanamide445 70

388.553-[5-(allylsulfanyl)-4-isobutyl-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide389 71

506.603-[5-[(4-fluorobenzyl)-sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide507 72

491.063-{4-(3-chlorophenyl)-5-[(2-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-phenylethyl)propanamide491 73

438.593-[4-benzyl-5-(butylsulfanyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide439 74

442.563-[5-[(3-fluorobenzyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-isobutylpropanamide443 75

466.653-{5-[(3,5-dimethylbenzyl)sulfanyl]-4-isobutyl-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)propanamide467 76

484.593-[5-[(4-fluorobenzyl)sulfanyl]4-(tetrahydro-2-furanylmethyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide485 77

428.99N-butyl-3-{5-[(3-chlorobenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}propanamide429 78

459.013-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-methylphenyl)-4H-1,2,4-triazol-3-yl]-N-(3-methoxypropyl)propanamide459 79

457.043-{4-(3-chlorophenyl)-5-[(3,5-dimethylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-isobutylpropanamide457 80

422.59N-butyl-3-[5-[(3-methylbenzyl)sulfanyl]-4-(3-methylphenyl)-4H-1,2,4-triazol-3-yl]propanamide423 81

436.58N-allyl-3-[5-[(3,5-dimethylbenzyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]propanamide437 82

485.053-{4-(3-chlorophenyl)-5-[(3,5-dimethylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(tetrahydro-2-furanylmethyl)propanamide485 83

442.973-[5-(allylsulfanyl)-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide443 84

497.623-[5-[(3-cyanobenzyl)sulfanyl]-4-(3-methylphenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide498 85

472.613-[4-benzyl-5-(benzylsulfanyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide473 86

505.083-{4-(4-chlorophenyl)-5-[(3,5-dimethylbenzyl)sulfanyl)-4H-1,2,4-triazol-3-yl}-N-(2-phenylethyl)propanamide505 87

494.573-[5-[(2-fluorobenzyl)sulfanyl]4-(4-fluorophenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide495 88

442.563-[5-[(4-fluorobenzyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-isobutylpropanamide443 89

443.013-[5-[(3-chlorobenzyl)sulfanyl)-4-(3-methylphenyl)-4H-1,2,4-triazol-3-yl]-N-isobutylpropanamide443 90

470.643-[5-[(3-methylbenzyl)sulfanyl]-4-(4-methylphenyl)-4H-1,2,4-triazol-3-yl]-N-(2-phenylethyl)propanamide471 91

482.60N-(2-methoxybenzyl)-3-{4-(3-methoxypropyl)-5-[2-oxo-2-phenylethyl)sulfanyl]-4H-1,2,4-triazol-3-yl}propanamide483 92

473.043-{4-(4-chlorophenyl)-5-[(3,5-dimethylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(3-methoxypropyl)propanamide473 93

428.533-[5-[(3-fluorobenzyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-propylpropanamide429 94

494.573-[5-[(4-fluorobenzyl)sulfanyl]-4-(4-fluorophenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide495 95

511.473-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-(2-phenylethyl)propanamide511 96

414.963-[5-(benzylsulfanyl)-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-propylpropanamide415 97

477.03N-benzyl-3-{4-(3-chlorophenyl)-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}propanamide477 98

529.463-[5-[(2-chloro-4-fluorobenzyl)sulfanyl]-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-(2-phenylethyl)propanamide529 99

512.083-{4-(3-chlorophenyl)-5-[4-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-[3-(2-oxo-1-pyrrolidinyl)propyl]propanamide512 100

459.013-{4-(4-chlorophenyl)-5-[(3,5-dimethylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-methoxyethyl)propanamide459 101

422.59N-isobutyl-3-[5-[(3-methylbenzyl)sulfanyl]-4-(4-methylphenyl)-4H-1,2,4-triazol-3-yl]propanamide423 102

446.98N-butyl-3-{4-(3-chlorophenyl)-5-[(3-fluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}propanamide447 103

441.003-{4-(3-chlorophenyl)-5-[3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(cyclopropylmethyl)propanamide441 104

472.583-[5-[(4-fluorobenzyl)sulfanyl]-4-(3-methoxypropyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide473 105

459.013-{4-(4-chlorophenyl)-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl]-N-(3-methoxypropyl)propanamide459 106

484.673-[5-[(3,5-dimethylbenzyl)sulfanyl]-4-(4-methylphenyl)-4H-1,2,4-triazol-3-yl]-N-(2-phenylethyl)propanamide485 107

474.603-[5-[(3-fluorobenzyl)sulfanyl]-4-(4-methylphenyl)-4H-1,2,4-triazol-3-yl]-N-(2-phenylethyl)propanamide475 108

450.653-{5-[(3,5-dimethylbenzyl)sulfanyl]-4-isobutyl-4H-1,2,4-triazol-3-yl}-N-(2-phenylethyl)propanamide451 109

505.083-{4-(3-chlorophenyl)-5-[(3,5-dimethylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-phenylethyl)propanamide505 110

507.063-{4-(3-chlorophenyl)-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(4-methoxybenzyl)propanamide507 111

406.553-{4-allyl-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-benzylpropanamide407 112

502.64N-(4-methoxybenzyl)-3-{4-(3-methoxyphenyl)-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}propanamide503 113

414.503-{5-[(2-fluorobenzyl)sulfanyl]4-methyl-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)propanamide415 114

495.023-{4-(3-chlorophenyl)-5-[(2-fluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-phenylethyl)propanamide495 115

495.023-{4-(4-chlorophenyl)-5-[(3-fluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-phenylethyl)propanamide495 116

502.043-{4-(4-chlorophenyl)-5-[(3-cyanobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl)-N-(2-phenylethyl)propanamide502 117

501.583-[5-[(3-cyanobenzyl)sulfanyl]4-(4-fluorophenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide502 118

426.97N-allyl-3-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-methylphenyl)-4H-1,2,4-triazol-3-yl]propanamide427 119

459.013-{4-(4-chlorophenyl)-5-[(4-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(3-methoxypropyl)propanamide459 120

422.55N-allyl-3-{4-(3-methoxyphenyl)-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}propanamide423 121

496.983-(4-(3-chlorophenyl)-5-{[4-(trifluoromethyl)benzyl]sulfanyl}-4H-1,2,4-triazol-3-yl)-N-isobutylpropanamide497 122

480.633-[5-[(3,5-dimethylbenzyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-(tetrahydro-2-furanylmethyl)propanamide481 123

454.593-[5-(butylsulfanyl)-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide455 124

443.01N-butyl-3-{4-(4-chlorophenyl)-5-[(4-methylbenzyl)sulfanyl)-4H-1,2,4-triazol-3-yl]propanamide443 125

426.51N-allyl-3-[5-[(3-fluorobenzyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]propanamide427 126

512.083-{4-(4-chlorophenyl)-5-[(4-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-[3-(2-oxo-1-pyrrolidinyl)propyl]propananmide512 127

448.953-{5-[(2-chloro-4-fluorobenzyl)sulfanyl]-4-methyl-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)propanamide449 128

466.653-[5-[(3,5-dimethylbenzyl)sulfanyl]-4-(3-methoxypropyl)-4H-1,2,4-triazol-3-yl]-N-(2-phenylethyl)propanamide467 129

511.023-{4-(3-chlorophenyl)-5-[(4-fluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(4-methoxybenzyl)propanamide511 130

446.98N-butyl-3-{4-(3-chlorophenyl)-5-[(2-fluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}propanamide447 131

408.573-[5-[(3-methylbenzyl)sulfanyl]-4-(4-methylphenyl)-4H-1,2,4-triazol-3-yl]-N-propylpropanamide409 132

432.953-{4-(3-chlorophenyl)-5-[(3-fluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-propylpropanamide433 133

521.083-{4-(3-chlorophenyl)-5-[3,5-dimethylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(4-methoxybenzyl)propanamide521 134

494.663-[5-[(3,5-dimethylbenzyl)sulfanyl]-4-(tetrahydro-2-furanylmethyl)-4H-1,2,4-triazol-3-yl]-N-(4-methoxybenzyl)propanamide495 135

491.063-{4-(4-chlorophenyl)-5-[(2-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-phenylethyl)propanamide491 136

438.59N-isobutyl-3-{4-(3-methoxyphenyl)-5-[(3-methylbenzyl)sulfanyl)-4H-1,2,4-triazol-3-yl}propanamide439 137

507.064-{5-[(3-chlorobenzyl)sulfanyl}-4-phenyl-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)butanamide507 138

541.504-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)butanamide542 139

537.084-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)butanamide537 140

511.47N-benzyl-4-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]butanamide511 141

516.66N-(2-methoxybenzyl)-4-{4-(3-methoxyphenyl)-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}butanamide517 142

503.074-([5-[{(3-chlorobenzyl)sulfanyl]-4-(3-methoxypropyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)butanamide503 143

487.074-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-methoxypropyl)-4H-1,2,4-triazol-3-yl]-N-(2-phenylethyl)butanamide487 144

525.054-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-(4-fluorobenzyl)butanamide525 145

530.694-[5-[(3,5-dimethylbenzyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)butanamide531 146

504.63N-(4-fluorobenzyl)-4-{4-(3-methoxyphenyl)-5-[(4-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}butanamide505 147

520.634-[5-[(3-fluorobenzyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)butanamide521 148

500.664-{4-(3-methoxyphenyl)-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-phenylethyl)butanamide501 149

508.64N-(1,3-benzodioxol-5-ylmethyl)-4-(4-(3-methoxypropyl)-5-{[(2E)-3-phenyl-2-propenyl]sulfanyl}-4H-1,2,4-triazol-3-yl)butanamide509 150

525.054-{4-(3-chlorophenyl)-5-[(2-fluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)butanamide525 151

486.64N-benzyl-4-{4-(3-methoxyphenyl)-5-[(2-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}butanamide487 152

507.06N-benzyl-4-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]butanamide570 153

504.63N-(4-fluorobenzyl)-4-{4-(3-methoxyphenyl)-5-[(2-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}butanamide505 154

473.044-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-isobutylbutanamide473 155

580.55N-(4-fluorobenzyl)-4-{4-(3-methoxyphenyl)-5-[(2,3,4,5,6-pentafluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}butanamide581 156

521.084-{4-(3-chlorophenyl)-5-[(2-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)butanamide521 157

459.014-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-propylbutanamide459 158

520.634-[5-[(4-fluorobenzyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)butanamide521 159

529.464-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-(4-fluorobenzyl)butanamide529 160

537.084-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-(4-methoxybenzyl)butanamide537 161

505.474-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-(tetrahydro-2-furanylmethyl)butanamide505 162

505.08N-benzyl-4-{4-(3-chlorophenyl)-5-[(3,5-dimethylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}butanamide505 163

504.634-[5-[(3-fluorobenzyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-(2-phenylethyl)butanamide505 164

532.074-[3-chlorophenyl)-5-[(3-cyanobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)butanamide532 165

541.504-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-(4-methoxybenzyl)butanamide542 166

527.654-[5-[(3-cyanobenzyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)butanamide528 167

452.62N-isobutyl-4-{4-(3-methoxyphenyl)-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}butanamide453 168

516.66N-(4-methoxybenzyl)-4-{4-(3-methoxyphenyl)-5-[(4-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}butanamide517 169

514.694-[5-[(3,5-dimethylbenzyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-(2-phenylethyl)butanamide515 170

491.06N-benzyl-4-{4-(3-chlorophenyl)-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}butanamide491 171

559.494-[5-[(2-chloro-4-fluorobenzyl)sulfanyl]-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)butanamide559 172

461.41N-allyl-4-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]butanamide461 173

477.464-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-isobutylbutanamide477 174

518.664-[5-[(3,5-dimethylbenzyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-(4-fluorobenzyl)butanamide519 175

495.02N-benzyl-4-{4-(3-chlorophenyl)-5-[(3-fluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}butanamide495 176

477.03N-benzyl-4-{5-(benzylsulfanyl)-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]butanamide477 177

521.084-{4-(3-chlorophenyl)-5-[(2-phenylethyl)sulfanyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)butanamide521 178

480.674-[5-[(3,5-dimethylbenzyl)sulfanyl]-4-(3-methoxypropyl)-4H-1,2,4-triazol-3-yl]-N-(2-phenylethyl)butanamide481 179

486.64N-benzyl-4-{4-(3-methoxyphenyl)-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}butanamide487 180

463.434-[5-{(3-chlorobenzyl)sulfanyl]-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-propylbutanamide463 181

509.054-{4-(3-chlorophenyl)-5-[(2-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(4-fluorobenzyl)butanamide509 182

452.624-[5-[(3,5-dimethylbenzyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-propylbutanamide453 183

508.694-[5-[(cyclohexylmethyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)butanamide509 184

555.535-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)pentanamide555 185

521.084-{5-[(3-chlorobenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)pentanamide521 186

496.67N-(2-methoxybenzyl)-5-{4-(3-methoxypropyl)-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}pentanamide497 187

491.485-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-isobutylpentanamide491 188

464.634-{4-allyl-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)pentanamide465 189

528.72N-(2-methoxybenzyl)-5-[5-[(3-methylbenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]pentanamide529 190

500.66N-(2-methoxybenzyl)-5-{5-[3-methylbenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}pentanamide501 191

539.075-{4-(3-chlorophenyl)-5-[(2-fluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)pentanamide539 192

500.645-[5-[(3-fluorobenzyl)sulfanyl]-4-(3-methoxypropyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)pentanamide501 193

543.495-[5-[(3-chlorobenzyl)sulfanyl)-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-(4-fluorobenzyl)pentanamide543 194

478.705-[5-[(3,5-dimethylbenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]--N-isobutylpentanamide479 195

491.06N-benzyl-5-{5-[(3-chlorobenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}pentanamide491 196

504.635-{5-[(3-fluorobenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)pentanamide505 197

482.655-[5-(benzylsulfanyl)-4-(3-methoxypropyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxypropyl)pentanamide483 198

505.08N-benzyl-5-{4-(3-chlorophenyl)-5-[(4-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}pentanamide505 199

478.665-{4-allyl-5-[(3,5-dimethylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)pentanamide479 200

485.055-{4-allyl-5-[(3-chlorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)pentanamide485 201

486.645-[5-(benzylsulfanyl)-4-phenyl-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)pentanamide487 202

450.615-[4-allyl-5-(benzyl-sulfanyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)pentanamide451 203

526.755-[5-[(3,5-dimethylbenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]-N-(2-phenylethyl)pentanamide527 204

549.145-[5-[(3-chlorobenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)pentanamide549 205

505.08N-benzyl-5-{4-(3-chlorophenyl)-5-[(2-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}pentanamide505 206

468.604-allyl-5-[(3-fluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)pentanamide469 207

542.70N-(1,3-benzodioxol-5-ylmethyl)-5-[5-[(2-methylbenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]pentanamide543 208

542.755-[5-[(3,5-dimethylbenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)pentanamide543 209

504.635-{5-[(2-fluorobenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)pentanamide505 210

537.105-[5-[(3-chlorobenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]-N-(4-fluorobenzyl)pentanamide537 211

581.01N-benzyl-5-{4-(3-chlorophenyl)-5-[(2,3,4,5,6-pentafluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}pentanamide581 212

510.705-[5-[(3,5-dimethylbenzyl)sulfanyl]-4-(3-methoxypropyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)pentanamide511 213

499.085-{4-(3-chlorophenyl)-5-[(4-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(tetrahydro-2-furanylmethyl)pentanamide499 214

525.50N-benzyl-5-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]pentanamide526 215

509.055-{5-[(3-chlorobenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}-N-(4-fluorobenzyl)pentanamide509 216

546.095-{4-(3-chlorophenyl)-5-[(3-cyanobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)pentanamide546 217

499.085-{4-(3-chlorophenyl)-5-[(2-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(tetrahydro-2-furanylmethyl)pentanamide499 218

521.085-[5-(benzylsulfanyl)-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)pentanamide521 219

452.625-{5-[(3,5-dimethylbenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}-N-(2-methoxyethyl)pentanamide453 220

512.725-[5-[(3-methylbenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]-N-(2-phenylethyl)pentanamide513 221

475.44N-allyl-5-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]pentanamide475 222

509.475-[5-[(2-chloro-4-fluorobenzyl)sulfanyl]-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-isobutylpentanamide509 223

450.65N-butyl-5-{5-[(3,5-dimethylbenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}pentanamide451 224

611.045-{4-(3-chlorophenyl)-5-[(2,3,4,5,6-pentafluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)pentanamide611 225

519.715-{5-[(3,5-dimethylbenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}-N-[3-(2-oxo-1-pyrrolidinyl)propyl]pentanamide520 226

514.695-{5-[(3,5-dimethylbenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)pentanamide515 227

498.675-[5-[(3,5-dimethylbenzyl)sulfanyl]-4-(3-methoxypropyl)-4H-1,2,4-triazol-3-yl]-N-(4-fluorobenzyl)pentanamide499 228

471.075-[5-[(3-chlorobenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]-N-propylpentanamide471 229

539.075-{4-(3-chlorophenyl)-5-[(3-fluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)pentanamide539 230

464.635-{4-allyl-5-[(4-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)pentanamide465 231

532.685-[5-[(2-fluorobenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)pentanamide533 232

484.64N-(4-fluorobenzyl)-5-{4-(3-methoxypropyl)-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}pentanamide485 233

527.045-{4-(3-chlorophenyl)-5-[(2-fluorobenzyl)sulfanyl)-4H-1,2,4-triazol-3-yl}-N-(4-fluorobenzyl)pentanamide527 234

535.115-{4-(3-chlorophenyl)-5-[(4-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(4-methoxybenzyl)pentanamide535 235

500.66N-(4-methoxybenzyl)-5-{5-[(4-methylbenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}pentanamide501 236

513.105-[5-[(3-chlorobenzyl)sulfanyl]-4-(tetrahydro-2-furanylmethyl)-4H-1,2,4-triazol-3-yl]-N-(2-phenylethyl)pentanamide513 237

471.075-{4-(3-chlorophenyl)-5-[(4-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-isobutylpentanamide471 238

514.695-{4-(3-methoxyphenyl)-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-phenylethyl)pentanamide515 239

537.485-[5-[(2-chloro-4-fluorobenzyl)sulfanyl]-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-(tetrahydro-2-furanylmethyl)pentanamide537 240

470.64N-benzyl-5-{5-[(3-methylbenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}pentanamide471 241

543.49N-benzyl-5-[5-[(2-chloro-4-fluorobenzyl)sulfanyl]4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]pentanamide543 242

516.68N-(4-fluorobenzyl)-5-[5-[(2-methylbenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]pentanamide517 243

485.095-[5-[(3-chlorobenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]-N-isobutylpentanamide485 244

434.61N-(cyclopropylmethyl)-5-{5-[(3-methylbenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}pentanamide435 245

452.625-{4-(3-methoxyphenyl)-5-[(4-methylbenzyl)sulfanyl)-4H-1,2,4-triazol-3-yl}-N-propylpentanamide453 246

466.655-{5-[(3,5-dimethylbenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}-N-(3-methoxypropyl)pentanamide467 247

512.72N-benzyl-5-[5-[(3,5-dimethylbenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]pentanamide513 248

484.675-{5-[(3-methylbenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}-N-(2-phenylethyl)pentanamide485 249

488.63N-(4-fluorobenzyl)-5-{5-[(3-methylbenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-pentanamide489 250

448.63N-(cyclopropylmethyl)-5-{5-[(3,5-dimethylbenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}pentanamide449 251

436.625-{5-[(3,5-dimethylbenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}-N-propylpentanamide437 252

528.725-[5-[(3,5-dimethylbenzyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-(2-phenylethyl)pentanamide529 253

505.08N-benzyl-5-{4-(3-chlorophenyl)-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}pentanamide505 254

470.64N-benzyl-5-{5-[(4-methylbenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}pentanamide471 255

535.115-{4-(3-chlorophenyl)-5-[(2-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(4-methoxybenzyl)pentanamide535 256

533.145-{4-(3-chlorophenyl)-5-[(3,5-dimethylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-phenylethyl)pentanamide533 257

554.165-{4-(3-chlorophenyl)-5-[(3,5-dimethylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-[3-(2-oxo-1-pyrrolidinyl)propyl]pentanamide554 258

519.115-{4-(3-chlorophenyl)-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-phenylethyl)pentanamide519 259

532.685-[5-[(3-fluorobenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)pentanamide533 260

535.115-{4-(3-chlorophenyl)-5-[(2-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)pentanamide535 261

452.605-{4-allyl-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(4-fluorobenzyl)pentanamide453 262

519.07N-benzyl-5-{4-(3-chlorophenyl)-5-[(2-oxo-2-phenylethyl)sulfanyl]-4H-1,2,4-triazol-3-yl}pentanamide519 263

540.135-{4-(3-chlorophenyl)-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-[3-(2-oxo-1-pyrrolidinyl)propyl]pentanamide264

464.63N-(cyclopropylmethyl)-5-{4-(3-methoxyphenyl)-5-[(2-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}pentanamide465 265

505.685-{5-[(3-methylbenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}-N-[3-(2-oxo-1-pyrrolidinyl)propyl]pentanamide506 266

455.02N-allyl-5-{4-(3-chlorophenyl)-5-[(4-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}pentanamide455 267

493.43N-allyl-5-[5-[(2-chloro-4-fluorobenzyl)sulfanyl]-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]pentanamide493 268

471.075-{4-(3-chlorophenyl)-5-[(2-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-isobutylpentanamide471 269

488.63N-(4-fluorobenzyl)-5-{5-[(4-methylbenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}pentanamide489 270

501.095-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-methoxypropyl)-4H-1,2,4-triazol-3-yl]-N-(2-phenylethyl)pentanamide501 271

489.065-[5-[(2-chloro-4-fluorobenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]-N-propylpentanamide489 272

516.07N-benzyl-5-{4-(3-chlorophenyl)-5-[(3-cyanobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}pentanamide516 273

477.465-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-propylpentanamide477 274

438.59N-(2-methoxyethyl)-5-{5-[(3-methylbenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}pentanamide439 275

559.66N-[3-(2-oxo-1-pyrrolidinyl)propyl]-5-(4-phenyl-5-{[4-(trifluoromethyl)benzyl]sulfanyl}-4H-1,2,4-triazol-3-yl)pentanamide560 276

498.695-{5-[(3,5-dimethylbenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}-N-(2-phenylethyl)pentanamide499 277

484.67N-benzyl-5-{5-[(3,5-dimethylbenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}pentanamide485 278

516.68N-(4-fluorobenzyl)-5-[5-[(4-methylbenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]pentanamide517 279

549.095-{4-(3-chlorophenyl)-5-[(2-oxo-2-phenylethyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(4-methoxybenzyl)pentanamide549 280

478.66N-(cyclopropylmethyl)-5-[5-[(3,5-dimethylbenzyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]pentanamide479 281

436.62N-butyl-5-{5-[(3-methylbenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}pentanamide437 282

535.715-{4-(3-methoxyphenyl)-5-[(4-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-[3-(2-oxo-1-pyrrolidinyl)propyl]pentanamide536 283

474.605-[5-(benzylsulfanyl)-4-phenyl-4H-1,2,4-triazol-3-yl]-N-(4-fluorobenzyl)pentanamide475 284

535.115-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-(2-phenylethyl)pentanamide535 285

532.685-[5-[(4-fluorobenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)pentanamide533 286

434.61N-allyl-5-{5-[(3,5-dimethylbenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}pentanamide435 287

500.66N-(2-methoxybenzyl)-5-{5-[(4-methylbenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}pentanamide501 288

491.48N-butyl-5-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl}pentanamide491 289

489.475-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-(cyclopropylmethyl)pentanamide489 290

516.68N-(4-fluorobenzyl)-5-[5-[(3-methylbenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]pentanamide517 291

488.58N-(cyclopropylmethyl)-5-(4-phenyl-5-{[4-(trifluoromethyl)benzyl]sulfanyl}-4H-1,2,4-triazol-3-yl)pentanamide489 292

466.625-{4-allyl-5-[(3,5-dimethylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl]-N-(4-fluorobenzyl)pentanamide467 293

464.68N-isobutyl-5-[5-[(2-methylbenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]pentanamide465 294

549.745-[5-[(3,5-dimethylbenzyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-[3-(2-oxo-1-pyrrolidinyl)propyl]pentanamide550 295

573.525-[5-[(2-chloro-4-fluorobenzyl)sulfanyl]-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)pentanamide574 296

422.595-{5-[(3-methylbenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}-N-propylpentanamide423 297

485.055-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-(cyclopropylmethyl)pentanamide485 298

523.075-{4-(3-chlorophenyl)-5-[(4-fluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-phenylethyl)pentanamide523 299

468.62N-(2-methoxyethyl)-5-{4-(3-methoxyphenyl)-5-[3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}pentanamide469 300

534.065-{4-(3-chlorophenyl)-5-[3-cyanobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(4-fluorobenzyl)pentanamide534 301

457.045-{5-[(3-chlorobenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}-N-isobutylpentanamide457 302

505.085-[5-(benzylsulfanyl)-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-(2-phenylethyl)pentanamide505 303

530.95N-allyl-5-{4-(3-chlorophenyl)-5-[(2,3,4,5,6-pentafluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}pentanamide531 304

528.72N-(2-methoxybenzyl)-5-[5-[(2-methylbenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]pentanamide529 305

530.715-[5-[(3,5-dimethylbenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]-N-(4-fluorobenzyl)pentanamide531 306

436.62N-isobutyl-5-{5-[(4-methylbenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}pentanamide437 307

436.62N-isobutyl-5-{5-[(3-methylbenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}pentanamide437 308

519.715-{4-benzyl-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-[3-(2-oxo-1-pyrrolidinyl)propyl]pentanamide520 309

466.65N-benzyl-5-{4-(3-methoxypropyl)-5-[(3-methylbenzyl)sulfanyl)-4H-1,2,4-triazol-3-yl}pentanamide467 310

546.995-{4-(3-chlorophenyl)-5-[(2,3,4,5,6-pentafluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-isobutylpentanamide547 311

604.64N-(4-methoxybenzyl)-5-[5-[(2,3,4,5,6-pentafluorobenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]pentanamide605 312

491.06N-benzyl-5-[5-(benzylsulfanyl)-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]pentanamide491 313

423.025-[5-(butylsulfanyl)-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-isobutylpentanamide423 314

464.63N-(cyclopropylmethyl)-5-{4-(3-methoxyphenyl)-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}pentanamide465 315

462.665-{4-allyl-5-[3,5-dimethylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-phenylethyl)pentanamide463 316

542.755-[5-[(3,5-dimethylbenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]-N-(4-methoxybenzyl)pentanamide543 317

509.05N-benzyl-5-{4-(3-chlorophenyl)-5-[(2-fluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}pentanamide509 318

493.465-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxyethyl)pentanamide493 319

464.63N-(cyclopropylmethyl)-5-{4-(3-methoxyphenyl)-5-[(4-methylbenzyl)sulfanyl)-4H-1,2,4-triazol-3-yl}pentanamide465 320

523.075-{4-(3-chlorophenyl)-5-[(2-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl)-N-(4-fluorobenzyl)pentanamide523 321

513.105-[5-[(3-chlorobenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]-N-(tetrahydro-2-furanylmethylpentanamide513 322

611.045-{4-(3-chlorophenyl)-5-[(2,3,4,5,6-pentafluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(4-methoxybenzyl)pentanamide611 323

424.995-[5-(butylsulfanyl)-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxyethyl)pentanamide425 324

456.61N-benzyl-5-[5-(benzylsulfanyl)-4-phenyl-4H-1,2,4-triazol-3-yl]pentanamide457 325

450.655-{5-[(3,5-dimethylbenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}-N-isobutylpentanamide451 326

504.635-{5-[(4-fluorobenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)pentanamide505 327

533.745-{4-benzyl-5-[(3,5-dimethylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-[3-(2-oxo-1-pyrrolidinyl)propyl]pentanamide534 328

483.085-(4-(3-chlorophenyl)-5-{[(2E)-3-phenyl-2-propenyl]sulfanyl}-4H-1,2,4-triazol-3-yl)-N-isobutylpentanamide483 329

523.075-{4-(3-chlorophenyl)-5-[(3-fluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl]-N-(2-phenylethyl)pentanamide523 330

450.655-[5-[(2-methylbenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]-N-propylpentanamide451 331

455.02N-allyl-5-{4-(3-chlorophenyl)-5-[(2-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}pentanamide455 332

490.59N-butyl-5-(4-phenyl-5-{[4-(trifluoromethyl)benzyl]sulfanyl}-4H-1,2,4-triazol-3-yl)pentanamide491 333

485.055-{5-[(3-chlorobenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}-N-(tetrahydro-2-furanylmethyl)pentanamide485 334

500.645-[5-[(4-fluorobenzyl)sulfanyl]-4-(3-methoxypropyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)pentanamide501 335

452.62N-(3-methoxypropyl)-5-{5-[(3-methylbenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}pentanamide453 336

478.66N-isobutyl-5-[5-[(2-oxo-2-phenylethyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]pentanamide479 337

488.635-{5-[(3-fluorobenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl)-N-(2-phenylethyl)pentanamide489 338

492.57N-(2-methoxyethyl}-5-(4-phenyl-5-{[4-(trifluoromethyl)benzyl]sulfanyl}-4H-1,2,4-triazol-3-yl)pentanamide493 339

464.635-{5-[(4-methylbenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}-N-(tetrahydro-2-furanylmethyl)pentanamide465 340

471.075-{4-(3-chlorophenyl)-5-[(3,5-dimethylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-propylpentanamide471 341

471.07N-butyl-5-{4-(3-chlorophenyl)-5-[(4-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}pentanamide471 342

507.485-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-(3-methoxypropyl)pentanamide507 343

513.065-{4-(3-chlorophenyl)-5-[(2-oxo-2-phenylethyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(tetrahydro-2-furanylmethyl)pentanamide513 344

478.665-{5-[(3,5-dimethylbenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl)-N-(tetrahydro-2-furanylmethyl)pentanamide479 345

506.59N-(3-methoxypropyl)-5-(4-phenyl-5-{[4-(trifluoromethyl)benzyl]sulfanyl}-4H-1,2,4-triazol-3-yl)pentanamide507 346

539.075-{4-(3-chlorophenyl)-5-](4-fluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)pentanamide539 347

594.105-(4-(3-chlorophenyl)-5-{[4-(trifluoromethyl)benzyl]sulfanyl}-4H-1,2,4-triazol-3-yl)-N-[3-(2-oxo-1-pyrrolidinyl)propyl]pentanamide594 348

520.65N-(4-fluorobenzyl)-5-[5-[(2-fluorobenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]pentanamide521 349

567.135-[5-[(2-chloro-4-fluorobenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)pentanamide567 350

498.69N-benzyl-5-[5-[(3-methylbenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]pentanamide499 351

546.095-{4-(3-chlorophenyl)-5-[(3-cyanobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(4-methoxybenzyl)pentanamide546 352

485.055-{4-(3-chlorophenyl)-5-[(2-oxo-2-phenylethyl)sulfanyl]-4H-1,2,4-triazol-3-yl)-N-isobutylpentanamide485 353

452.625-{4-benzyl-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-methoxyethyl)pentanamide453 354

563.12N-(1,3-benzodioxol-5-ylmethyl)-5-[5-[(3-chlorobenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]pentanamide563 355

519.495-[5-[(3-chlorobenzyl)sulfanyl)-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-(tetrahydro-2-furanylmethyl)pentanamide519 356

528.72N-(4-methoxybenzyl)-5-[5-[(2-methylbenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]pentanamide529 357

475.035-{4-(3-chlorophenyl)-5-[(2-fluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-isobutylpentanamide475 358

476.575-(4-phenyl-5-{[4-(trifluoromethyl)benzyl]sulfanyl}-4H-1,2,4-triazol-3-yl)-N-propylpentanamide477 359

468.605-{4-allyl-5-[(4-fluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)pentanamide469 360

514.695-[5-(benzylsulfanyl)-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)pentanamide515 361

509.05N-benzyl-5-{4-(3-chlorophenyl)-5-[(3-fluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}pentanamide509 362

540.73N-(2-methoxybenzyl)-5-(4-(2-phenylethy1)-5-{[(2E)-3-phenyl-2-propenyl]sulfanyl}-4H-1,2,4-triazol-3-yl)pentanamide541 363

457.045-{4-(3-chlorophenyl)-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-propylpentanamide457 364

487.075-{4-(3-chlorophenyl)-5-[(4-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(3-methoxypropyl)pentanamide487 365

485.09N-butyl-5-{4-(3-chlorophenyl)-5-[(3,5-dimethylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}pentanamide485 366

470.64N-benzyl-5-{5-[(2-methylbenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}pentanamide471 367

482.655-[5-[(3,5-dimethylbenzyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxyethyl)pentanamide483 368

485.095-{4-(3-chlorophenyl)-5-[(3,5-dimethylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-isobutylpentanamide485 369

487.075-[5-(butylsulfanyl)-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)pentanamide487 370

455.025-{4-allyl-5-[(3-chlorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-benzylpentanamide455 371

511.655-{5-[(3-cyanobenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)pentanamide512 372

434.615-{4-allyl-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-benzylpentanamide435 373

546.67N-(1,3-benzodioxol-5-ylmethyl)-5-[5-[(2-fluorobenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]pentanamide547 374

499.035-{4-allyl-5-[(3-chlorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(1,3-benzodioxol-5-ylmethyl)pentanamide499 375

450.655-[5-[(3-methylbenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]-N-propylpentanamide451 376

464.605-[5-[(2-fluorobenzyl)sulfanyl]-4-(tetrahydro-2-furanylmethyl)-4H-1,2,4-triazol-3-yl]-N-(3-methoxypropyl)pentanamide465 377

528.72N-(2-methoxybenzyl)-5-[5-[(4-methylbenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]pentanamide529 378

567.135-[5-[(2-chloro-4-fluorobenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]-N-(4-methoxybenzyl)pentanamide567 379

443.015-{5-[(3-chlorobenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}-N-propylpentanamide443 380

492.695-[5-[(4-methylbenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]-N-(tetrahydro-2-furanylmethyl)pentanamide493 381

535.115-{4-(3-chlorophenyl)-5-[(2-phenylethyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)pentanamide535 382

507.465-[5-[(2-chloro-4-fluorobenzyl)sulfanyl]-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-(cyclopropylmethyl)pentanamide507

Example 383 Preparation of a Pharmaceutical Formulation

The following Formulation examples illustrate representativepharmaceutical compositions according to the present invention being.

Formulation 1—Tablets

A triazole compound of Formula I is admixed as a dry powder with a drygelatin binder in an approximate 1:2 weight ration. A minor amount ofmagnesium stearate is added as a lubricant. The mixture is formed into240-270 mg tablets (80-90 mg of active triazole compound per tablet) ina tablet press.

Formulation 2—Capsules

A triazole compound of Formula I is admixed as a dry powder with astarch diluent in an approximate 1:1 weight ratio. The mixture is filledinto 250 mg capsules (125 mg of active triazole compound per capsule).

Formulation 3—Liquid

A triazole compound of Formula I (1250 mg), sucrose (1.75 g) and xanthangum (4 mg) are blended, passed through a No. 10 mesh U.S. sieve, andthen mixed with a previously prepared solution of microcrystallinecellulose and sodium carboxymethyl cellulose (11:89, 50 mg) in water.Sodium benzoate (10 mg), flavor, and color are diluted with water andadded with stirring. Sufficient water is then added to produce a totalvolume of 5 mL.

Formulation 4—Tablets

A triazole compound of Formula I is admixed as a dry powder with a drygelatin binder in an approximate 1:2 weight ratio. A minor amount ofmagnesium stearate is added as a lubricant. The mixture is formed into450-900 mg tablets (150-300 mg of active triazole compound) in a tabletpress.

Formulation 5—Injection

A triazole compound of Formula I is dissolved in a buffered sterilesaline injectable aqueous medium to a concentration of approximately 5mg/ml.

Example 384 Biological Assays

The compounds according to Formula I may be subjected to the followingassays:

a) In vitro Competition Binding Assay on hOT Receptor with ScintillationProximity Assay (18).

This assay allows to determine the affinity of the test compounds forthe human Oxytocin (hOT) receptor. Membranes from HEK293EBNA (cellsexpressing the hOT receptor) were suspended in buffer containing 50 mMTris-HCl, pH 7.4, 5 mM MgCl2 and 0.1% BSA (w/v). The membranes (2-4 fg)were mixed with 0.1 mg SPA bead coated with wheat-germ aglutinin(WGA-PVT-Polyethylene Imine beads from Amersham) and 0.2 DM of theradiolabelled [¹²⁵I]-OVTA (OVTA being Omithin Vasoactive, an analogue ofOT for competitive binding experiments). Non-specific binding wasdetermined in the presence of 1 μM Oxytocin. The total assay volume was100 μL. The plates (Corning® NBS plate) were incubated at roomtemperature for 30 min and counted on a Mibrobeta® plate scintillationcounter. Competitive binding was performed in presence of compounds offormula (1) at the following concentrations: 30 μM, 10 μM, 1 μM, 300 nM,100 nM 10 nM, 1 nM, 100 pM, 10 pM. The competitive binding data wereanalysed using the iterative, nonlinear, curve-fitting program, “Prism”(GraphPad Software, Inc).

The ability of triazole derivatives of formula (I) to inhibit thebinding of ¹²⁵I-OVTA to the OT-receptor was assessed using the abovedescribed in vitro biological assay. Representative values for someexample compounds are given in Table 3 where the binding affinity of thecompounds is expressed by the inhibition constant (Ki; μM). From thesevalues, it can be derived that said test compounds according to formulaI do show a significant binding to the oxytocin receptor.

TABLE 3 Binding Affinity Example hOT-R No. IUPAC-Name (Ki [μM]) 13-[5-[(3-chlorobenzyl)sulfanyl]-4-(3- 0.045methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-(2- methoxybenzyl)propanamide 53-[5-[(3-fluorobenzyl)sulfanyl]-4-(4- 0.127methylphenyl)-4H-1,2,4-triazol-3-yl]-N-(2- methoxybenzyl)propanamide 33-{4-(3-chlorophenyl)-5-[(3- 0.134methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)propanamide 16 N-(2-methoxybenzyl)-3-{4-(3- 0.197methoxyphenyl)-5-[(3- methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}propanamide 9 3-[5-(benzylsulfanyl)-4-(4-methylphenyl)- 0.2054H-1,2,4-triazol-3-yl]-N-(2- methoxybenzyl)propanamide 83-[5-[(3-chlorobenzyl)sulfanyl]-4-(3- 0.229methylphenyl)-4H-1,2,4-triazol-3-yl]-N-(2- methoxybenzyl)propanamide 15N-butyl-3-[5-[(3-chlorobenzyl)sulfanyl]-4-(3- 0.245chlorophenyl)-4H-1,2,4-triazol-3- yl]propanamide 6N-(2-methoxybenzyl)-3-{4-(4- 0.246methylbenzyl)-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}propanamide 43-[5-[(3-chlorobenzyl)sulfanyl]-4-(3- 0.326methoxypropyl)-4H-1,2,4-triazol-3-yl]-N-(2- methoxybenzyl)propanamide 113-{4-(3-chlorophenyl)-5-[(4- 0.329fluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)propanamide 123-[5-(benzylsulfanyl)-4-(3-chlorophenyl)- 0.4394H-1,2,4-triazol-3-yl]-N-(2- methoxybenzyl)propanamide 1845-[5-[(3-chlorobenzyl)sulfanyl]-4-(3- 0.481chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-(2- methoxybenzyl)pentanamide 189N-(2-methoxybenzyl)-5-[5-[(3- 0.515methylbenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]pentanamide 1855-{5-[(3-chlorobenzyl)sulfanyl]-4-phenyl- 0.6034H-1,2,4-triazol-3-yl}-N-(2- methoxybenzyl)pentanamide 1374-{5-[(3-chlorobenzyl)sulfanyl]-4-phenyl- 2.5504H-1,2,4-triazol-3-yl}-N-(2- methoxybenzyl)butanamide

b) In vitro Competition Binding Assay on hV1a Receptor withScintillation Proximity Assay (18)

This assay allows the determination of the affinity of the testcompounds for the V1a receptor. Membranes from CHO cells expressing thehV1a receptor are suspended in buffer containing 50 mM Tris-HCl, pH 7.4,5 mM MgCl₂ and 0.1% BSA (w/v). The membranes (5-10 μg) are mixed with0.2 mg SPA bead coated with wheat-germ aglutinin (WGA beads fromAmersham) and 0.03 nM of the radiolabelled [¹²⁵I]-LVA (LVA being LinearVasopressin Antagonist and is an analogue of AVP for competitive bindingexperiments). Non-specific binding is determined in the presence of 1 μMAVP. The total assay volume is 100 μl. The plates (Corning® NBS plate)are incubated at room temperature for 2 hours and counted on aMibrobeta® plate scintillation counter. Competitive binding can beperformed in presence of test compounds at the following concentrations:30 μM, 10 μM, 1 μM, 300 nM, 100 nM, 10 nM, 1 nM, 100 pM, 10 pM. Thecompetitive binding data can then be analysed using the iterative,nonlinear, curve-fitting program, “Prism” (GraphPad Software, Inc).

The binding affinities to the V_(1a) receptor of the triazolederivatives claimed in the formula I can be measured using the abovedescribed in vitro biological assay.

c) Functional Assay No. 1: Inhibition of Oxytocin MediatedCa²⁺-mobilization by FLIPR® (Fluorimetric Imaging Plate Reader)

The action of OT on the OT-receptor triggers a complex cascade of eventsin the cell which leads to an increase in the intra-cytoplasmic Ca²⁺concentration. This increase in Ca²⁺ concentration results from bothcalcium release from the sarcoplasmic reticulum (calcium stores) intothe cytoplasm and from calcium influx from the extracellular spacethrough Ca²⁺ channels. This Ca²⁺ mobilization into the cytoplasmtriggers the contractile machinery of the myometrial cells which leadsto uterine contractions (4 and 19).

This assay allows the measurement of the inhibition of OT/OT-R mediatedcalcium mobilization by test compounds of formula (1).

FLIPR® is a fluorimetric imaging device using a laser (Argon-ion laser)for simultaneous illumination and reading (cooled CCD camera) of eachwell of a 96-well-plate, thus enabling rapid measurements on a largenumber of samples.

Preparing the plates: FLIPR-plates were pre-coated with PLL(Poly-L-Lysine) 10 μg/ml+0.1% gelatine to attach HEK293EBNA cells (HumanEmbryonic Kidney cells expressing the hOT receptor) and incubated for 30min up to 2 days at 37° C. The cells were plated out into 96-well-plates(60000 cells/well).

Labelling with fluo-4: 50 μg of fluo-4 (Ca2+ sensitive fluorescent dye)were dissolved in 20 μl pluronic acid (20% in DMSO). The dissolvedfluo-4 was then diluted in 10 ml DMEM (Dubecco's Minimal EssentialMedium)-F12 culture medium. The plates were washed one time withDMEM-F12 medium 100 μl of the fluo-4 containing-DMEM-F12 medium wereadded to the HEK-cells which were incubated for 1.5-2 h in thisfluorescent medium. Fluo-4 is taken up by the cytoplasm of the cells.

Buffer: 145 mM NaCl, 5 mM KCl, 1 mM MgCl₂, 10 mM Hepes, 10 mM Glucose,EGTA Ethylene-bis oxyethylene nitrilo tetraacetic acid). The pH wasadjusted to 7.4.

Performance of the assay: A minimum of 80 μl/well of compounds offormula (I) (5×) in the above buffer (1×) were prepared(96-well-plates). The compounds of formula (I) were added to the96-well-plates at different concentrations (30 μM, 10 μM, 1 μM, 300 nM,100 nM, 10 nM, 1 nM, 100 pM, 10 pM). OT was added at a concentration of40 nM.

The relative fluorescence of Fluo (λ_(ex)=488 nm, λ_(em)=590 nm) is thenmeasured by the FLIPR in presence or absence of compounds of formula(I). The fluorescence of the marker being sensitive to the amount ofCa²⁺, the Ca²⁺ movements can be detected. Then, it can be determined theability of compounds of formula (I) to antagonize the oxytocin-inducedintracellular Ca²⁺-mobilization mediated by the oxytocin receptor.

The activities of the triazole derivatives according to formula I wereassessed using the above described in vitro biological assay.Representative values for some example compounds are given in Table 4.The values refer to the concentration of the test compounds according toformula I necessary to antagonize by 50% the OT/OTR intracellularCa²⁺-mobilization. From the values, it can be derived that said examplecompounds according to formula I do exhibit a significant activity asoxytocin receptor antagonists.

TABLE 4 Inhibition of Ca2+ Chemical mobilisation; hOT-R StructureIUPAC-Name IC50 [μM] 1 3-[5-[(3-chlorobenzyl)sulfanyl]-4-(3- 0.026methoxyphenyl)-4H-1,2,4-triazol-3-yl]- N-(2-methoxybenzyl)propanamide185 5-{5-[(3-chlorobenzyl)sulfanyl]-4- 0.058phenyl-4H-1,2,4-triazol-3-yl}-N-(2- methoxybenzyl)pentanamide 1374-{5-[(3-chlorobenzyl)sulfanyl]-4- 0.486phenyl-4H-1,2,4-triazol-3-yl}-N-(2- methoxybenzyl)butanamide

d) Functional Assay No. 1: Inhibition of Vasopressin-MediatedCa²⁺-Mobilization by FLIPR® (Fluorimetric Imaging Plate Reader)

The action of AVP on the V₁-receptor triggers a complex cascade ofevents in the cell which leads to an increase in the intra-cytoplasmicCa²⁺ concentration. This increase in Ca²⁺ concentration results fromboth calcium release from the sarcoplasmic reticulum (calcium stores)into the cytoplasm and from calcium influx from the extracellular spacethrough Ca²⁺ channels. This Ca²⁺ mobilization into the cytoplasmtriggers the contractile machinery of the myometrial cells which leadsto uterine contractions (4 and 19).

This assay can be used to measure the inhibition of AVP/V_(1a)-Rmediated calcium mobilization by test compounds of formula (I).

FLIPR® is a fluorimetric imaging device using a laser (Argon-ion laser)for simultaneous illumination and reading (cooled CCD camera) of eachwell of a 96-well-plate, thus enabling rapid measurements on a largenumber of samples.

Preparing the plates: FLIPR-plates are pre-coated with PLL(Poly-L-Lysine) 10 μg/ml+0.1% gelatine to attach the CHO cells(expessing hV_(1a)) and incubated for 30 min up to 2 days at 37° C. Thecells are plated out into 96-well plates (60000 cells/well).

Labelling with fluo-4: 50 μg fluo-4 (fluorescent marker) is dissolved in20 μl pluronic acid (20% in DMSO). The dissolved fluo-4 is then dilutedin 10 ml DMEM (Dubecco's Minimal Essential Medium-F12 medium. The mediumis removed from the plates, followed by one wash with DMEM-F12 medium.100 μl of the DMEM-F12 medium containing fluo-4 are added and the cellsincubated for 1-1.5 h (CHO-cells).

Buffer: 145 mM NaCl, 5 mM KCl, 1 mM MgCl₂, 10 mM Hepes, 10 mM Glucose,EGTA (Ethylene-bis oxyethylene nitrilo tetraacetic acid). Adjust to pH7.4.

Performance of the assay: A minimum of 80 μl/well of antagonists (5×) inthe above buffer (1×) is prepared (96-well plates). The antagonists canbe added to the well-plates at different concentrations (30 μM, 10 μM, 1μM, 300 nK 100 nM, 10 nK, 1 nM 100 pM, 10 pM). AVP is added at aconcentration of 40 nM.

The relative fluorescence of Fluo-4 (λ_(ex)=488 nm, μ_(em)=590 nm) canthen be measured by the FLIPR in presence or absence of compounds offormula (1). The fluorescence of the marker being sensitive to theamount of Ca²⁺, the Ca²⁺ movements can be detected.

In the same way as for the FLIPR assay with OT receptor expressingcells, the capacity of the triazole derivatives according to formula I,to effectively antagonize AVP-induced intracellular Ca²⁺-mobilizationmediated by the action of AVP at the V_(1a)-receptor, can be assessedusing the above described in vitro biological assay.

e) Functional Assay No. 2: Inhibition of IP3 (InositolTri-Phosphate)-Synthesis in HEK/EBNA-OTR Cells

The interaction of OT on the OT-receptor leads to the IP3 synthesis,second messenger for Ca²⁺ release from sarcoplasmic reticulum, involvedin the uterine contraction triggering process (4).

This assay can be used to show the inhibition of the OT/OT-R mediatedIP3 synthesis by using test compounds of formula (I).

Stimulation of the cells: HEK/EBNA OTR (rat or human) cells are platedout into costar 12-well plates, and equilibrated for 15-24 h with 4μCi/ml radiolabelled [³H]-Inositol with 1% FCS (0.5 ml/well) and withoutinositol supplement. The medium containing the label is aspirated. DMEMmedium (without FCS, inositol), 20 mM Hepes(4-(2-hydroxyethyl)-1-piperazine-ethane-sulphonic acid), 1 mg/ml BSAcontaining 10 mM LiCl (freshly prepared), are added and incubated for10-15 min at 37° C. The agonist (i.e. oxytocin used at a concentrationof 10 nM) and the antagonists (i.e. the tests compounds of formula (1)can be used in a concentration of 10 μM, 1 μM, 300 nM, 100 nM, 10 nM, 1nM, 100 pM, 10 pM, 3 pM) can be added at the required time (15-45 min),followed by aspiration of the medium In the presence of OT, theradiolabelled inositol is converted to radiolabelled IP3. AntagonizingOT at the OT-receptor inhibits the IP3 formation.

The amount of the radiolabelled IP3 may be determined through theensuing work-up. The reaction is stopped with 1 ml STOP-solution (i.e.0.4 M perchloric acid), and let sit for 5-10 min at Room Temperature.Then, 0.8 ml are transferred into tubes containing 0.4 ml ofneutralizing solution (0.72 M KOH/0.6M KHCO₃), and the tubes vortexedand kept in the cold at least for 2 h.

Separation of IP's: The samples are spun in a table top centrifuge at3000-4000 rpm for 15 min. 1 ml of the supernatant is transferred to newtubes containing 2.5 ml H₂O. Packed resin (Dowex AG1X8) is equilibratedwith 20 ml H₂O, and the whole samples are poured onto the chromatographycolumns, thus separating the mixture. To remove free inositol, twowashes with 10 ml H₂O are carried out.

Elution of total IP's: Elution is achieved using 3 ml 1M ammoniumformate/0.1M formic acid. The eluant is collected in scintillationcounting tubes, after the addition of 7 ml of scintillation liquid. Theamount of [³H]-IP3 is determined by a scintillating counter.

The ability of compounds of formula(I) to effectively antagonizeoxytocin-induced IP3-synthesis mediated by the oxytocin receptor, can beassessed using the above described in vitro biological assay.

f) In vivo Model for Inhibition of Uterine Contractions

The assay evaluates the biological effect of tested compounds in an invivo model of preterm labor, premature birth.

Non-pregnant Charles River CD (SD) BR female rats (9-10 weeks old,200-250 g) were treated at 18 and 24 hours before the experiment with250 μg/kg, i.p. diethylstilbestrol (DES). For the assay, the animal wasanaesthetised with urethane (1.75 g/kg, i.p.) and placed on ahomeothermic operating table. The trachea was isolated and cannulatedwith a suitable polyethylene (PE) tubing. A midline incision at thehypogastrium level was made and one uterine horn exposed, its cephalicend cannulated with a PE240 tubing and, after filling the internalcavity with 0.2 ml of sterile physiological saline, connected to a“Gemini” amplifying/recording system via a P23ID Gould Statham pressuretransducer.

One jugular vein was isolated, cannulated with a PE60 tubing andconnected to a butterfly needle to provide an i.v. route ofadministration of the test compounds via a dispensing syringe.

In the case of intraduodenal administration of the test compounds, theduodenum can be isolated and similarly cannulated through a smallincision in its wall.

One carotid artery was also isolated and cannulated with PE60 catheterand connected to a suitable syringe for blood sample collection.

After a stabilization period and throughout the experiment, the samedose of oxytocin was repeatedly injected intravenously at 30-minintervals. When reproducible contractile responses of the uterus to thesame OT stimulus (selected dose of oxytocin) were obtained, the dose ofthe test or of the reference (vehicle) was administered. Furtherinjection cycles of the same dose of oxytocin, were continued (OTinjections at 30-min intervals) for a suitable time after treatment toassess the inhibitory effects and the reversibility of these effects.

The contractile response of the uterus to oxytocin was quantified bymeasuring the intra-uterine pressure and the number of contractions. Theeffect of the reference and test compounds was evaluated by comparingpre- and post-treatment pressure values. In addition, at 2, 30, 90 and210 minutes after test compound administration, a 0.5-ml blood samplewas withdrawn from the cannulated carotid artery of each experimentalanimal. Plasma was obtained by standard laboratory procedure and theresulting samples were stored at −20° C.

The activities of the triazole derivatives claimed in the Formula I canbe assessed using the above described in vivo biological assay.Representative values for one example compound are given in Table 5. Thevalues refer to the capacity of the example compound according toFormula I to effectively antagonize oxytocin-induced uterinecontractions in the rat. From the values shown in Table 5 it can bederived that said example test compound according to Formula I doesexhibit a significant activity as tocolytic, i.e. uterine-relaxing,agent.

TABLE 5 % Reduction of Chemical Uterine Doses Structure IUPAC-NameContraction [mg/kg] 1 3-[5-[(3-chlorobenzyl)sulfanyl]- 16.9 ± 5.1 104-(3-methoxyphenyl)-4H-1,2,4- triazol-3-yl]-N-(2-methoxybenzyl)propanamide

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1. The triazole derivative of Formula I:

its geometrical isomers, its optically active forms as enantiomers,diastereomers, mixtures of these and its racemate forms, as well assalts thereof, wherein: R¹ and R² are independently selected from thegroup consisting of H, C₁-C₆-alkyl, aryl C₁-C₆-alkyl,heteroarylC₁-C₆-alkyl, C₃-C₆-cycloalkyl C₁-C₆-alkyl andC₃-C₆-heterocycloalkyl C₁-C₆-alkyl; R¹ and R², together with thenitrogen atom they are linked to, form a substituted or unsubstituted5-8-membered saturated, partially unsaturated or aromatic ringcontaining optionally one or more additional heteroatoms selected fromO, N, S; A is C(O); R³ is selected from the group consisting of H,C₁-C₆-alkyl, aryl C₁-C₆-alkyl, heteroaryl C₁-C₆-alkyl, aryl, heteroaryl,C₃-C₆-cycloalkyl C₁-C₆-alkyl, C₃-C₆-heterocycloalkyl C₁-C₆-alkyl,C₂-C₆-alkenyl; B is S; R⁴ and R⁵ are selected from the group consistingof H, C₁-C₆-alkyl, aryl C₁-C₆-alkyl, heteroaryl C₁-C₆-alkyl, acyl, arylacyl, heteroaryl acyl, C₃-C₆-cycloalkyl C₁-C₆-alkyl,C₃-C₆-heterocycloalkyl C₁-C₆-alkyl, C₂-C₆-alkenyl; n is an integer from2 to
 10. 2. The triazole derivative according to claim 1, wherein A iscarbonyl.
 3. The triazole derivative according to claim 1, wherein B issulfur.
 4. The triazole derivative according to claim 1, wherein n is aninteger from 2, 3 or
 4. 5. The triazole derivative according to claim 1,wherein A is carbonyl, B is sulfur and n is an integer from 2, 3 or 4.6. A triazole derivative according to claim 1, selected from the groupconsisting of:3-{4-benzyl-5-[(3-chlorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)propanamide,3-{4-(3-chlorophenyl)-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)propanamide,3-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-methoxypropyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide,3-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide,3-[5-[(3-fluorobenzyl)sulfanyl]-4-(4-methylphenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide,N-(2-methoxybenzyl)-3-{4-(4-methylbenzyl)-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}propanamide,3-{5-[(3-fluorobenzyl)sulfanyl]-4-isobutyl-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)propanamide,3-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-methylphenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide,3-[5-(benzylsulfanyl)-4-(4-methylphenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide,3-[5-(benzylsulfanyl)-4-isobutyl-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide,3-{4-(3-chlorophenyl)-5-[(4-fluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)propanamide,3-[5-(benzylsulfanyl)-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide,3-{4-isobutyl-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)propanamide,N-(2-methoxybenzyl)-3-[5-[(3-methylbenzyl)sulfanyl]-4-(tetrahydro-2-furanylmethyl)-4H-1,2,4-triazol-3-yl]propanamide,N-butyl-3-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]propanamide,N-(2-methoxybenzyl)-3-{4-(3-methoxyphenyl)-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}propanamide,3-{5-[(3-chlorobenzyl)sulfanyl]-4-methyl-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)propanamide,3-[5-[(3-fluorobenzyl)sulfanyl]-4-(tetrahydro-2-furanylmethyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide,3-{4-allyl-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)propanamide,3-[5-[(3-fluorobenzyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide,3-[5-(butylsulfanyl)-4-(3-methoxypropyl)-4H-1,2,4-triazol-3-yl]-N-(4-methoxybenzyl)propanamide,N-benzyl-3-{4-(3-methoxypropyl)-5-[(2-phenoxyethyl)sulfanyl]-4H-1,2,4-triazol-3-yl}propanamide,3-{4-benzyl-5-[(2-fluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)propanamide,3-[5-[(3-chlorobenzyl)sulfanyl]-4-(4-fluorophenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide,3-[5-(benzylsulfanyl)-4-(4-fluorophenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide,3-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-(cyclopropylmethyl)propanamide,3-[5-[(3-cyanobenzyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide,3-[5-(benzylsulfanyl)-4-(tetrahydro-2-furanylmethyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide,N-(2-methoxybenzyl)-3-{4-(3-methoxypropyl)-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}propanamide,3-[4-allyl-5-(benzylsulfanyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide,3-[5-[(3-fluorobenzyl)sulfanyl]-4-(3-methoxypropyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide,3-{4-(4-fluorophenyl)-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)propanamide,3-[5-(benzylsulfanyl)-4-(3-methoxypropyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide,3-[5-[(3-fluorobenzyl)sulfanyl]-4-(4-fluorophenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide,3-{4-allyl-5-[(3-fluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)propanamide,3-{4-(3-chlorophenyl)-5-[(3,5-dimethylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)propanamide,3-{4-(3-chlorophenyl)-5-[(3-fluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-isobutylpropanamide,3-[5-[(3,5-dimethylbenzyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide,3-{5-[(2-chloro-4-fluorobenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}-N-(2-furylmethyl)propanamide,3-[5-[(3-fluorobenzyl)sulfanyl]-4-(4-methylbenzyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide,3-{4-(3-chlorophenyl)-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-propylpropanamide,3-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxyethyl)propanamide,3-[5-(allylsulfanyl)-4-(4-methylbenzyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide,3-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-(3-methoxypropyl)propanamide,3-{4-(3-chlorophenyl)-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-isobutylpropanamide,N-(2-methoxybenzyl)-3-[5-[(3-methylbenzyl)sulfanyl]-4-(4-methylphenyl)-4H-1,2,4-triazol-3-yl]propanamide,3-[5-[(2-fluorobenzyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide,3-[5-(benzylsulfanyl)-4-(4-methylbenzyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide,3{4-benzyl-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)propanamide,N-allyl-3-{4-(3-chlorophenyl)-5-[(3,5-dimethylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}propanamide,3-[5-[(2-fluorobenzyl)sulfanyl]-4-(3-methylphenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide,3-{5-[(4-fluorobenzyl)sulfanyl]-4-isobutyl-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)propanamide,3-[5-[(3,5-dimethylbenzyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-isobutylpropanamide,3-{4-(3-chlorophenyl)-5-[(4-fluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-isobutylpropanamide,N-butyl-3-[5-[(3-chlorobenzyl)sulfanyl]-4-(4-chlorophenyl)-4H-1,2,4-triazol-3-yl]propanamide,3-[5-[(3-chlorobenzyl)sulfanyl]-4-(4-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-(2-phenylethyl)propanamide,3-[5-[(2-fluorobenzyl)sulfanyl]-4-(3-methoxypropyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide,3-{4-(3-chlorophenyl)-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(tetrahydro-2-furanylmethyl)propanamide,3-{4-(4-chlorophenyl)-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-phenylethyl)propanamide,3-{4-(3-chlorophenyl)-5-[(3-cyanobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-phenylethyl)propanamide,N-(4-fluorobenzyl)-3-[5-[(2,3,4,5,6-pentafluorobenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]propanamide,3-{4-allyl-5-[(4-fluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)propanamide,3-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-methylphenyl)-4H-1,2,4-triazol-3-yl]-N-(cyclopropylmethyl)propanamide,3-[5-[(3-chlorobenzyl)sulfanyl]-4-(tetrahydro-2-furanylmethyl)-4H-1,2,4-triazol-3-yl]-N-(2-phenylethyl)propanamide,3-[5-(benzylsulfanyl)-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide,3-{4-allyl-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(tetrahydro-2-furanylmethyl)propanamide,3-[5-(allylsulfanyl)-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide,N-butyl-3-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-methylphenyl)-4H-1,2,4-triazol-3-yl]propanamide,3-{4-(4-chlorophenyl)-5-[(4-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-methoxyethyl)propanamide,3-[5-(allylsulfanyl)-4-isobutyl-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide,3-[5-[(4-fluorobenzyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide,3-{4-(3-chlorophenyl)-5-[(2-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-phenylethyl)propanamide,3-[4-benzyl-5-(butylsulfanyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide,3-[5-[(3-fluorobenzyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-isobutylpropanamide,3-{5-[(3,5-dimethylbenzyl)sulfanyl]-4-isobutyl-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)propanamide.3-[5-[(4-fluorobenzyl)sulfanyl]-4-(tetrahydro-2-furanylmethyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide,N-butyl-3-{5-[(3-chlorobenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}propanamide,3-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-methylphenyl)-4H-1,2,4-triazol-3-yl]-N-(3-methoxypropyl)propanamide,3-{4-(3-chlorophenyl)-5-[(3,5-dimethylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-isobutylpropanamide,N-butyl-3-[5-[(3-methylbenzyl)sulfanyl]-4-(3-methylphenyl)-4H-1,2,4-triazol-3-yl]propanamide,N-allyl-3-[5-[(3,5-dimethylbenzyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]propanamide,3-{4-(3-chlorophenyl)-5-[(3,5-dimethylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(tetrahydro-2-furanylmethyl)propanamide,3-[5-(allylsulfanyl)-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide,3-[5-[(3-cyanobenzyl)sulfanyl]-4-(3-methylphenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide,3-[4-benzyl-5-(benzylsulfanyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide,3-{4-(4-chlorophenyl)-5-[(3,5-dimethylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-phenylethyl)propanamide,3-[5-[(2-fluorobenzyl)sulfanyl]-4-(4-fluorophenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide,3-[5-[(4-fluorobenzyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-isobutylpropanamide,3-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-methylphenyl)-4H-1,2,4-triazol-3-yl]-N-isobutylpropanamide,3-[5-[(3-methylbenzyl)sulfanyl]-4-(4-methylphenyl)-4H-1,2,4-triazol-3-yl]-N-(2-phenylethyl)propanamide,N-(2-methoxybenzyl)-3-{4-(3-methoxypropyl)-5-[(2-oxo-2-phenylethyl)sulfanyl]-4H-1,2,4-triazol-3-yl}propanamide,3-{4-(4-chlorophenyl)-5-[(3,5-dimethylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(3-methoxypropyl)propanamide,3-[5-[(3-fluorobenzyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-propylpropanamide,3-[5-[(4-fluorobenzyl)sulfanyl]-4-(4-fluorophenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide,3-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-(2-phenylethyl)propanamide,3-[5-(benzylsulfanyl)-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-propylpropanamide,N-benzyl-3-{4-(3-chlorophenyl)-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}propanamide,3-[5-[(2-chloro-4-fluorobenzyl)sulfanyl]-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-(2-phenylethyl)propanamide,3-{4-(3-chlorophenyl)-5-[(4-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-[3-(2-oxo-1-pyrrolidinyl)propyl]propanamide,3-{4-(4-chlorophenyl)-5-[(3,5-dimethylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-methoxyethyl)propanamide,N-isobutyl-3-[5-[(3-methylbenzyl)sulfanyl]-4-(4-methylphenyl)-4H-1,2,4-triazol-3-yl]propanamide,N-butyl-3-{4-(3-chlorophenyl)-5-[(3-fluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}propanamide,3-{4-(3-chlorophenyl)-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(cyclopropylmethyl)propanamide,3-[5-[(4-fluorobenzyl)sulfanyl]-4-(3-methoxypropyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide,3-{4-(4-chlorophenyl)-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(3-methoxypropyl)propanamide,3-[5-[(3,5-dimethylbenzyl)sulfanyl]-4-(4-methylphenyl)-4H-1,2,4-triazol-3-yl]-N-(2-phenylethyl)propanamide,3-[5-[(3-fluorobenzyl)sulfanyl]-4-(4-methylphenyl)-4H-1,2,4-triazol-3-yl]-N-(2-phenylethyl)propanamide,3-{5-[(3,5-dimethylbenzyl)sulfanyl]-4-isobutyl-4H-1,2,4-triazol-3-yl}-N-(2-phenylethyl)propanamide,3-{4-(3-chlorophenyl)-5-[(3,5-dimethylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-phenylethyl)propanamide,3-{4-(3-chlorophenyl)-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(4-methoxybenzyl)propanamide,3-{4-allyl-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-benzylpropanamide,N-(4-methoxybenzyl)-3-{4-(3-methoxyphenyl)-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}propanamide,3-{5-[(2-fluorobenzyl)sulfanyl]-4-methyl-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)propanamide,3-{4-(3-chlorophenyl)-5-[(2-fluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-phenylethyl)propanamide,3-{4-(4-chlorophenyl)-5-[(3-fluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-phenylethyl)propanamide,3-{4-(4-chlorophenyl)-5-[(3-cyanobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-phenylethyl)propanamide,3-[5-[(3-cyanobenzyl)sulfanyl]-4-(4-fluorophenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide,N-allyl-3-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-methylphenyl)-4H-1,2,4-triazol-3-yl]propanamide,3-{4-(4-chlorophenyl)-5-[(4-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(3-methoxypropyl)propanamide,N-allyl-3-{4-(3-methoxyphenyl)-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}propanamide,3-(4-(3-chlorophenyl)-5-{[4-(trifluoromethyl)benzyl]sulfanyl}-4H-1,2,4-triazol-3-yl)-N-isobutylpropanamide,3-[5-[(3,5-dimethylbenzyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-(tetrahydro-2-furanylmethyl)propanamide,3-[5-(butylsulfanyl)-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)propanamide,N-butyl-3-{4-(4-chlorophenyl)-5-[(4-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}propanamide,N-allyl-3-[5-[(3-fluorobenzyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]propanamide,3-{4-(4-chlorophenyl)-5-[(4-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-[3-(2-oxo-1-pyrrolidinyl)propyl]propanamide,3-{5-[(2-chloro-4-fluorobenzyl)sulfanyl]-4-methyl-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)propanamide,3-[5-[(3,5-dimethylbenzyl)sulfanyl]-4-(3-methoxypropyl)-4H-1,2,4-triazol-3-yl]-N-(2-phenylethyl)propanamide,3-{4-(3-chlorophenyl)-5-[(4-fluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(4-methoxybenzyl)propanamide,N-butyl-3-{4-(3-chlorophenyl)-5-[(2-fluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}propanamide,3-[5-[(3-methylbenzyl)sulfanyl]-4-(4-methylphenyl)-4H-1,2,4-triazol-3-yl]-N-propylpropanamide,3-{4-(3-chlorophenyl)-5-[(3-fluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-propylpropanamide,3-{4-(3-chlorophenyl)-5-[(3,5-dimethylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(4-methoxybenzyl)propanamide,3-[5-[(3,5-dimethylbenzyl)sulfanyl]-4-(tetrahydro-2-furanylmethyl)-4H-1,2,4-triazol-3-yl]-N-(4-methoxybenzyl)propanamide,3-{4-(4-chlorophenyl)-5-[(2-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-phenylethyl)propanamide,N-isobutyl-3-{4-(3-methoxyphenyl)-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}propanamide,4-{5-[(3-chlorobenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)butanamide,4-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)butanamide,4-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)butanamide,N-benzyl-4-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]butanamide,N-(2-methoxybenzyl)-4-{4-(3-methoxyphenyl)-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}butanamide,4-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-methoxypropyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)butanamide,4-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-methoxypropyl)-4H-1,2,4-triazol-3-yl]-N-(2-phenylethyl)butanamide,4-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-(4-fluorobenzyl)butanamide,4-[5-[(3,5-dimethylbenzyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)butanamide,N-(4-fluorobenzyl)-4-{4-(3-methoxyphenyl)-5-[(4-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}butanamide,4-[5-[(3-fluorobenzyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-2-methoxybenzyl)butanamide,4-{4-(3-methoxyphenyl)-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-phenylethyl)butanamide,N-(1,3-benzodioxol-5-ylmethyl)-4-(4-(3-methoxypropyl)-5-{[(2E)-3-phenyl-2-propenyl]sulfanyl}-4H-1,2,4-triazol-3-yl)butanamide,4-{4-(3-chlorophenyl)-5-[(2-fluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)butanamide,N-benzyl-4-{4-(3-methoxyphenyl)-5-[(2-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}butanamide,N-benzyl-4-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]butanamide,N-(4-fluorobenzyl)-4-{4-(3-methoxyphenyl)-5-[(2-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}butanamide,4-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-isobutylbutanamide,N-(4-fluorobenzyl)-4-{4-(3-methoxyphenyl)-5-[(2,3,4,5,6-pentafluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}butanamide,4-{4-(3-chlorophenyl)-5-[(2-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)butanamide,4-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-propylbutanamide,4-[5-[(4-fluorobenzyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)butanamide,4-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-(4-fluorobenzyl)butanamide,4-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-(4-methoxybenzyl)butanamide,4-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-(tetrahydro-2-furanylmethyl)butanamide,N-benzyl-4-{4-(3-chlorophenyl)-5-[(3,5-dimethylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}butanamide,4-[5-[(3-fluorobenzyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-(2-phenylethyl)butanamide,4-{4-(3-chlorophenyl)-5-[(3-cyanobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)butanamide,4-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-(4-methoxybenzyl)butanamide,4-[5-[(3-cyanobenzyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)butanamide,N-isobutyl-4-{4-(3-methoxyphenyl)-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}butanamide,N-(4-methoxybenzyl)-4-{4-(3-methoxyphenyl)-5-[(4-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}butanamide,4-[5-[(3,5-dimethylbenzyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-(2-phenylethyl)butanamide,N-benzyl-4-{4-(3-chlorophenyl)-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}butanamide,4-[5-[(2-chloro-4-fluorobenzyl)sulfanyl]-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)butanamide,N-allyl-4-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]butanamide,4-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-isobutylbutanamide,4-[5-[(3,5-dimethylbenzyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-(4-fluorobenzyl)butanamide,N-benzyl-4-{4-(3-chlorophenyl)-5-[(3-fluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}butanamide,N-benzyl-4-[5-(benzylsulfanyl)-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]butanamide,4-{4-(3-chlorophenyl)-5-[(2-phenylethyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)butanamide,4-[5-[(3,5-dimethylbenzyl)sulfanyl]-4-(3-methoxypropyl)-4H-1,2,4-triazol-3-yl]-N-(2-phenylethyl)butanamide,N-benzyl-4-{4-(3-methoxyphenyl)-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}butanamide,4-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-propylbutanamide,4-{4-(3-chlorophenyl)-5-[(2-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(4-fluorobenzyl)butanamide,4-[5-[(3,5-dimethylbenzyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-propylbutanamide,4-[5-[(cyclohexylmethyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)butanamide,5-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)pentanamide,5-{5-[(3-chlorobenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)pentanamide,N-(2-methoxybenzyl)-5-{4-(3-methoxypropyl)-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}pentanamide,5-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-isobutylpentanamide,5-{4-allyl-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)pentanamide,N-(2-methoxybenzyl)-5-[5-[(3-methylbenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]pentanamide,N-(2-methoxybenzyl)-5-{5-[(3-methylbenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}pentanamide,5-{4-(3-chlorophenyl)-5-[(2-fluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)pentanamide,5-[5-[(3-fluorobenzyl)sulfanyl]-4-(3-methoxypropyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)pentanamide,5-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-(4-fluorobenzyl)pentanamide,5-[5-[(3,5-dimethylbenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]-N-isobutylpentanamide,N-benzyl-5-{5-[(3-chlorobenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}pentanamide,5-{5-[(3-fluorobenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)pentanamide,5-[5-(benzylsulfanyl)-4-(3-methoxypropyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)pentanamide,N-benzyl-5-{4-(3-chlorophenyl)-5-[(4-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}pentanamide,5-{4-allyl-5-[(3,5-dimethylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)pentanamide,5-{4-allyl-5-[(3-chlorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)pentanamide,5-[5-(benzylsulfanyl)-4-phenyl-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)pentanamide,5-[4-allyl-5-(benzylsulfanyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)pentanamide,5-[5-[(3,5-dimethylbenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]-N-(2-phenylethyl)pentanamide,5-[5-[(3-chlorobenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)pentanamide,N-benzyl-5-{4-(3-chlorophenyl)-5-[(2-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}pentanamide,5-{4-allyl-5-[(3-fluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)pentanamide,N-(1,3-benzodioxol-5-ylmethyl)-5-[5-[(2-methylbenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]pentanamide,5-[5-[(3,5-dimethylbenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)pentanamide,5-{5-[(2-fluorobenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)pentanamide,5-[5-[(3-chlorobenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]-N-(4-fluorobenzyl)pentanamide,N-benzyl-5-{4-(3-chlorophenyl)-5-[(2,3,4,5,6-pentafluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}pentanamide,5-[5-[(3,5-dimethylbenzyl)sulfanyl]-4-(3-methoxypropyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)pentanamide,5-{4-(3-chlorophenyl)-5-[(4-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(tetrahydro-2-furanylmethyl)pentanamide,N-benzyl-5-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]pentanamide,5-{5-[(3-chlorobenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}-N-(4-fluorobenzyl)pentanamide,5-{4-(3-chlorophenyl)-5-[(3-cyanobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)pentanamide,5-{4-(3-chlorophenyl)-5-[(2-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(tetrahydro-2-furanylmethyl)pentanamide,5-[5-(benzylsulfanyl)-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)pentanamide,5-{5-[(3,5-dimethylbenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}-N-(2-methoxyethyl)pentanamide,5-[5-[(3-methylbenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]-N-(2-phenylethyl)pentanamide,N-allyl-5-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]pentanamide,5-[5-[(2-chloro-4-fluorobenzyl)sulfanyl]-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-isobutylpentanamide,N-butyl-5-{5-[(3,5-dimethylbenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}pentanamide,5-{4-(3-chlorophenyl)-5-[(2,3,4,5,6-pentafluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)pentanamide,5-{5-[(3,5-dimethylbenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}-N-[3-(2-oxo-1-pyrrolidinyl)propyl]pentanamide,5-{5-[(3,5-dimethylbenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)pentanamide,5-[5-[(3,5-dimethylbenzyl)sulfanyl]-4-(3-methoxypropyl)-4H-1,2,4-triazol-3-yl]-N-(4-fluorobenzyl)pentanamide,5-[5-[(3-chlorobenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]-N-propylpentanamide,5-{4-(3-chlorophenyl)-5-[(3-fluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)pentanamide,5-{4-allyl-5-[(4-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)pentanamide,5-[5-[(2-fluorobenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)pentanamide,N-(4-fluorobenzyl)-5-{4-(3-methoxypropyl)-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}pentanamide,5-{4-(3-chlorophenyl)-5-[(2-fluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(4-fluorobenzyl)pentanamide,5-{4-(3-chlorophenyl)-5-[(4-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(4-methoxybenzyl)pentanamide,N-(4-methoxybenzyl)-5-{5-[(4-methylbenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}pentanamide,5-[5-[(3-chlorobenzyl)sulfanyl]-4-(tetrahydro-2-furanylmethyl)-4H-1,2,4-triazol-3-yl]-N-(2-phenylethyl)pentanamide,5-{4-(3-chlorophenyl)-5-[(4-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-isobutylpentanamide,5-{4-(3-methoxyphenyl)-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-phenylethyl)pentanamide,5-[5-[(2-chloro-4-fluorobenzyl)sulfanyl]-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-(tetrahydro-2-furanylmethyl)pentanamide,N-benzyl-5-{5-[(3-methylbenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}pentanamide,N-benzyl-5-[5-[(2-chloro-4-fluorobenzyl)sulfanyl]-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]pentanamide,N-(4-fluorobenzyl)-5-[5-[(2-methylbenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]pentanamide,5-[5-[(3-chlorobenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]-N-isobutylpentanamide,N-(cyclopropylmethyl)-5-{5-[(3-methylbenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}pentanamide,5-{4-(3-methoxyphenyl)-5-[(4-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-propylpentanamide,5-{5-[(3,5-dimethylbenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}-N-(3-methoxypropyl)pentanamide,N-benzyl-5-[5-[(3,5-dimethylbenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]pentanamide,5-{5-[(3-methylbenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}-N-(2-phenylethyl)pentanamide,N-(4-fluorobenzyl)-5-{5-[(3-methylbenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}pentanamide,N-(cyclopropylmethyl)-5-{5-[(3,5-dimethylbenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}pentanamide,5-{5-[(3,5-dimethylbenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}-N-propylpentanamide,5-[5-[(3,5-dimethylbenzyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-(2-phenylethyl)pentanamide,N-benzyl-5-{4-(3-chlorophenyl)-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}pentanamide,N-benzyl-5-{5-[(4-methylbenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}pentanamide,5-{4-(3-chlorophenyl)-5-[(2-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(4-methoxybenzyl)pentanamide,5-{4-(3-chlorophenyl)-5-[(3,5-dimethylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-phenylethyl)pentanamide,5-{4-(3-chlorophenyl)-5-[(3,5-dimethylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-[3-(2-oxo-1-pyrrolidinyl)propyl]pentanamide,5-{4-(3-chlorophenyl)-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-phenylethyl)pentanamide,55-[5-[(3-fluorobenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)pentanamide,5-{4-(3-chlorophenyl)-5-[(2-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)pentanamide,5-{4-allyl-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(4-fluorobenzyl)pentanamide,N-benzyl-5-{4-(3-chlorophenyl)-5-[(2-oxo-2-phenylethyl)sulfanyl]-4H-1,2,4-triazol-3-yl}pentanamide,5-{4-(3-chlorophenyl)-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-[3-(2-oxo-1-pyrrolidinyl)propyl]pentanamide,N-(cyclopropylmethyl)-5-{4-(3-methoxyphenyl)-5-[(2-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}pentanamide,5-{5-[(3-methylbenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}-N-[3-(2-oxo-1-pyrrolidinyl)propyl]pentanamide,N-allyl-5-{4-(3-chlorophenyl)-5-[(4-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}pentanamide,N-allyl-5-[5-[(2-chloro-4-fluorobenzyl)sulfanyl]-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]pentanamide,5-{4-(3-chlorophenyl)-5-[(2-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-isobutylpentanamide,N-(4-fluorobenzyl)-5-{5-[(4-methylbenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}pentanamide,5-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-methoxypropyl)-4H-1,2,4-triazol-3-yl]-N-(2-phenylethyl)pentanamide,5-[5-[(2-chloro-4-fluorobenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]-N-propylpentanamide,N-benzyl-5-{4-(3-chlorophenyl)-5-[(3-cyanobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}pentanamide,5-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-propylpentanamide,N-(2-methoxyethyl)-5-{5-[(3-methylbenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}pentanamide,N-[3-(2-oxo-1-pyrrolidinyl)propyl]-5-(4-phenyl-5-{[4-(trifluoromethyl)benzyl]sulfanyl}-4H-1,2,4-triazol-3-yl)pentanamide,5-{5-[(3,5-dimethylbenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}-N-(2-phenylethyl)pentanamide,N-benzyl-5-{5-[(3,5-dimethylbenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}pentanamide,N-(4-fluorobenzyl)-5-[5-[(4-methylbenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]pentanamide,5-{4-(3-chlorophenyl)-5-[(2-oxo-2-phenylethyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(4-methoxybenzyl)pentanamide,N-(cyclopropylmethyl)-5-[5-[(3,5-dimethylbenzyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]pentanamide,N-butyl-5-{5-[(3-methylbenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}pentanamide,5-{4-(3-methoxyphenyl)-5-[(4-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-[3-(2-oxo-1-pyrrolidinyl)propyl]pentanamide,5-[5-(benzylsulfanyl)-4-phenyl-4H-1,2,4-triazol-3-yl]-N-(4-fluorobenzyl)pentanamide,5-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-(2-phenylethyl)pentanamide,5-[5-[(4-fluorobenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)pentanamide,N-allyl-5-{5-[(3,5-dimethylbenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}pentanamide,N-(2-methoxybenzyl)-5-{5-[(4-methylbenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}pentanamide,N-butyl-5-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]pentanamide,5-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-(cyclopropylmethyl)pentanamide,N-(4-fluorobenzyl)-5-[5-[(3-methylbenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]pentanamide,N-(cyclopropylmethyl)-5-(4-phenyl-5-{[4-(trifluoromethyl)benzyl]sulfanyl}-4H-1,2,4-triazol-3-yl)pentanamide,5-{4-allyl-5-[(3,5-dimethylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(4-fluorobenzyl)pentanamide,N-isobutyl-5-[5-[(2-methylbenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]pentanamide,5-[5-[(3,5-dimethylbenzyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-[3-(2-oxo-1-pyrrolidinyl)propyl]pentanamide,5-[5-[(2-chloro-4-fluorobenzyl)sulfanyl]-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)pentanamide,5-{5-[(3-methylbenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}-N-propylpentanamide,5-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-(cyclopropylmethyl)pentanamide,5-{4-(3-chlorophenyl)-5-[(4-fluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-phenylethyl)pentanamide,N-(2-methoxyethyl)-5-{4-(3-methoxyphenyl)-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}pentanamide,5-{4-(3-chlorophenyl)-5-[(3-cyanobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(4-fluorobenzyl)pentanamide5-{5-[(3-chlorobenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}-N-isobutylpentanamide,5-[5-(benzylsulfanyl)-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-(2-phenylethyl)pentanamide,N-allyl-5-{4-(3-chlorophenyl)-5-[(2,3,4,5,6-pentafluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}pentanamide,N-(2-methoxybenzyl)-5-[5-[(2-methylbenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]pentanamide,5-[5-[(3,5-dimethylbenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]-N-(4-fluorobenzyl)pentanamide,N-isobutyl-5-{5-[(4-methylbenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}pentanamide,N-isobutyl-5-{5-[(3-methylbenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}pentanamide,5-{4-benzyl-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-[3-(2-oxo-1-pyrrolidinyl)propyl]pentanamide,N-benzyl-5-{4-(3-methoxypropyl)-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}pentanamide,5-{4-(3-chlorophenyl)-5-[(2,3,4,5,6-pentafluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-isobutylpentanamide,N-(4-methoxybenzyl)-5-[5-[(2,3,4,5,6-pentafluorobenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]pentanamide,N-benzyl-5-[5-(benzylsulfanyl)-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]pentanamide,5-[5-(butylsulfanyl)-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-isobutylpentanamide,N-(cyclopropylmethyl)-5-{4-(3-methoxyphenyl)-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}pentanamide,5-{4-allyl-5-[(3,5-dimethylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-phenylethyl)pentanamide,5-[5-[(3,5-dimethylbenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]-N-(4-methoxybenzyl)pentanamide,N-benzyl-5-{4-(3-chlorophenyl)-5-[(2-fluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}pentanamide,5-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxyethyl)pentanamide,N-(cyclopropylmethyl)-5-{4-(3-methoxyphenyl)-5-[(4-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}pentanamide,5-{4-(3-chlorophenyl)-5-[(2-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(4-fluorobenzyl)pentanamide,5-[5-[(3-chlorobenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]-N-(tetrahydro-2-furanylmethyl)pentanamide,5-{4-(3-chlorophenyl)-5-[(2,3,4,5,6-pentafluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(4-methoxybenzyl)pentanamide,5-[5-(butylsulfanyl)-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxyethyl)pentanamide,N-benzyl-5-[5-(benzylsulfanyl)-4-phenyl-4H-1,2,4-triazol-3-yl]pentanamide,5-{5-[(3,5-dimethylbenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}-N-isobutylpentanamide,5-{5-[(4-fluorobenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)pentanamide,5-{4-benzyl-5-[(3,5-dimethylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-[3-(2-oxo-1-pyrrolidinyl)propyl]pentanamide,5-(4-(3-chlorophenyl)-5-{[(2E)-3-phenyl-2-propenyl]sulfanyl}-4H-1,2,4-triazol-3-yl)-N-isobutylpentanamide,5-{4-(3-chlorophenyl)-5-[(3-fluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-phenylethyl)pentanamide,5-[5-[(2-methylbenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]-N-propylpentanamide,N-allyl-5-{4-(3-chlorophenyl)-5-[(2-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}pentanamide,N-butyl-5-(4-phenyl-5-{[4-(trifluoromethyl)benzyl]sulfanyl}-4H-1,2,4-triazol-3-yl)pentanamide,5-{5-[(3-chlorobenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}-N-(tetrahydro-2-furanylmethyl)pentanamide,5-[5-[(4-fluorobenzyl)sulfanyl]-4-(3-methoxypropyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)pentanamide,N-(3-methoxypropyl)-5-{5-[(3-methylbenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}pentanamide,N-isobutyl-5-[5-[(2-oxo-2-phenylethyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]pentanamide,5-{5-[(3-fluorobenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}-N-(2-phenylethyl)pentanamide,N-(2-methoxyethyl)-5-(4-phenyl-5-{[4-(trifluoromethyl)benzyl]sulfanyl}-4H-1,2,4-triazol-3-yl)pentanamide,5-{5-[(4-methylbenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}-N-(tetrahydro-2-furanylmethyl)pentanamide,5-{4-(3-chlorophenyl)-5-[(3,5-dimethylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-propylpentanamide,N-butyl-5-{4-(3-chlorophenyl)-5-[(4-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}pentanamide,5-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-(3-methoxypropyl)pentanamide,5-{4-(3-chlorophenyl)-5-[(2-oxo-2-phenylethyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(tetrahydro-2-furanylmethyl)pentanamide,5-{5-[(3,5-dimethylbenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}-N-(tetrahydro-2-furanylmethyl)pentanamide,N-(3-methoxypropyl)-5-(4-phenyl-5-{[4-(trifluoromethyl)benzyl]sulfanyl}-4H-1,2,4-triazol-3-yl)pentanamide,5-{4-(3-chlorophenyl)-5-[(4-fluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)pentanamide,5-(4-(3-chlorophenyl)-5-{[4-(trifluoromethyl)benzyl]sulfanyl}-4H-1,2,4-triazol-3-yl)-N-[3-(2-oxo-1-pyrrolidinyl)propyl]pentanamide,N-(4-fluorobenzyl)-5-[5-[(2-fluorobenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]pentanamide,5-[5-[(2-chloro-4-fluorobenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)pentanamide,N-benzyl-5-[5-[(3-methylbenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]pentanamide,5-{4-(3-chlorophenyl)-5-[(3-cyanobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(4-methoxybenzyl)pentanamide,5-{4-(3-chlorophenyl)-5-[(2-oxo-2-phenylethyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-isobutylpentanamide,5-{4-benzyl-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-methoxyethyl)pentanamide,N-(1,3-benzodioxol-5-ylmethyl)-5-[5-[(3-chlorobenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]pentanamide,5-[5-[(3-chlorobenzyl)sulfanyl]-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-(tetrahydro-2-furanylmethyl)pentanamide,N-(4-methoxybenzyl)-5-[5-[(2-methylbenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]pentanamide,5-{4-(3-chlorophenyl)-5-[(2-fluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-isobutylpentanamide,5-(4-phenyl-5-{[4-(trifluoromethyl)benzyl]sulfanyl}-4H-1,2,4-triazol-3-yl)-N-propylpentanamide,5-{4-allyl-5-[(4-fluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)pentanamide,5-[5-(benzylsulfanyl)-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)pentanamide,N-benzyl-5-{4-(3-chlorophenyl)-5-[(3-fluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}pentanamide,N-(2-methoxybenzyl)-5-(4-(2-phenylethyl)-5-{[(2E)-3-phenyl-2-propenyl]sulfanyl}-4H-1,2,4-triazol-3-yl)pentanamide,5-{4-(3-chlorophenyl)-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-propylpentanamide,5-{4-(3-chlorophenyl)-5-[(4-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(3-methoxypropyl)pentanamide,N-butyl-5-{4-(3-chlorophenyl)-5-[(3,5-dimethylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}pentanamide,N-benzyl-5-{5-[(2-methylbenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}pentanamide,5-[5-[(3,5-dimethylbenzyl)sulfanyl]-4-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxyethyl)pentanamide,5-{4-(3-chlorophenyl)-5-[(3,5-dimethylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-isobutylpentanamide,5-[5-(butylsulfanyl)-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-(2-methoxybenzyl)pentanamide,5-{4-allyl-5-[(3-chlorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-benzylpentanamide,5-{5-[(3-cyanobenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)pentanamide,5-{4-allyl-5-[(3-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-benzylpentanamide,N-(1,3-benzodioxol-5-ylmethyl)-5-[5-[(2-fluorobenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]pentanamide,5-{4-allyl-5-[(3-chlorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(1,3-benzodioxol-5-ylmethyl)pentanamide,5-[5-[(3-methylbenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]-N-propylpentanamide,5-[5-[(2-fluorobenzyl)sulfanyl]-4-(tetrahydro-2-furanylmethyl)-4H-1,2,4-triazol-3-yl]-N-(3-methoxypropyl)pentanamide,N-(2-methoxybenzyl)-5-[5-[(4-methylbenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]pentanamide,5-[5-[(2-chloro-4-fluorobenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]-N-(4-methoxybenzyl)pentanamide,5-{5-[(3-chlorobenzyl)sulfanyl]-4-phenyl-4H-1,2,4-triazol-3-yl}-N-propylpentanamide,5-[5-[(4-methylbenzyl)sulfanyl]-4-(2-phenylethyl)-4H-1,2,4-triazol-3-yl]-N-(tetrahydro-2-furanylmethyl)pentanamide,5-{4-(3-chlorophenyl)-5-[(2-phenylethyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-N-(2-methoxybenzyl)pentanamideand5-[5-[(2-chloro-4-fluorobenzyl)sulfanyl]-4-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl]-N-(cyclopropylmethyl)pentanamide.7. A pharmaceutical composition comprising the triazole derivativeaccording to claim 1 and a pharmaceutically acceptable carrier, diluentor excipient thereof.
 8. A process for the preparation of the triazolederivative according to claim 1, comprising reacting a nucleophilicgroup of formula R⁴SH, wherein R⁴ is defined as in claim 1, with atriazole of formula XXXIII

wherein Z is a leaving group, and R¹, R², R³, A and n are defined as inclaim
 1. 9. The process according to claim 8, wherein the leaving groupZ of formula XXXIII is Cl.
 10. The process according to claim 8, whereinthe leaving group Z of formula XXXIII is SO₂Me.
 11. A triazolederivative of formula XXXIII:

wherein R¹ and R² are independently selected from the group consistingof H, C₁-C₆-alkyl, aryl C₁-C₆-alkyl, heteroarylC₁-C₆-alkyl,C₃-C₆-cycloalkyl C₁-C₆-alkyl, and C₃-C₆-heterocycloarlkyl C₁-C₆-alkyl;R¹ and R², together with the nitrogen atom they are linked to, form asubstituted or unsubstituted 5-8 membered saturated, partiallyunsaturated or aromatic ring containing optionally one or moreadditional heteroatoms selected from O, N, S; A is C(O); R³ is selectedfrom the group consisting of H, C₁-C₆-alkyl, aryl C₁-C₆-alkyl,heteroaryl C₁-C₆-alkyl, aryl, heteroaryl, C_(e)-C₆-cycloalkylC₁-C₆-alkyl, C₃-C₆-heterocycloalkyl C₁-C₆-alkyl, C₂-C₆-alkenyl, B is S;R⁴ and R⁵ are selected from the group consisting of H, C₁-C₆-alkyl, arylC₁-C₆-alkyl, heteroaryl C₁-C₆-alkyl, acyl, aryl acyl, heteroaryl acyl,C₃-C₆-cycloalkyl C₁-C₆-alkyl, C₃-C₆-heterocycloalkyl C₁-C₆-alkyl,C₂-C₆-alkenyl; n is an integer from 2 to 10, and Z is Cl or SO₂Me.